Good Day to All!
 I may be having issues with my new EVGA GTX 1080 SC and I was hoping for some help/guidance.  I and NOT overclocking the card yet, though I do have the Power % limit at 120%/85C.
Background:
...I had stopped playing Fallout 4 for a few weeks because of the multitude of game patches and played some old school Doom 3.
I had been searching for an in-stock GTX 1080 to upgrade from my 970 SLI setup and finally acquired one from Microcenter.
Prior to physically changing the cards I removed the (then) current drivers using the latest DDU in Safe-mode and then installed the new drivers (368.69) after a re-Boot.
I then loaded Fallout 4 to see how the new card performed.
Steam installed the latest patch and I loaded up my last save.
After about 20 mins...CTD.  Restarted game, loaded my last save...fast-travel to the inner city (more stressful for the card), moved 20 ft (in-game)...CTD.
Disabled/Uninstalled all Mods via Nexus Mod Manager (NMM)...still getting CTDs.
Searched online for any solutions and noticed there were a few others in the Steam forum having similar CTD issues after the latest patch. 
Deleted and regenerated my Fallout 4 ini files...no improvement.  Ran some other games and checked for issues with the card...Crysis 3, Witcher 3, Firestrike 1.1...no issues.
Uninstalled Fallout 4 completely...deleted and leftover files in the directory and isolated the save files...re-download Fallout 4 completely and installed with no Mods.
Started new character...get to Concord...get the Power Armor...CTD.
Examined the statistical graphs on MSI Afterburner looking for any weird spikes or strange behavior...nothing...card was not even at 60C..the only spike I saw was the GPU usage at the time of the crash spiked
to 100%....though other CTDs didn't seem to have that GPU usage spike.
In the 300 plus hours that I've played Fallout 4 with Mods installed, I've had almost no CTGs, now its like my late game Fallout 3 experience all over again...new cell loading CTD's (that was different computer)...I also had this type of CTD with a modded Skyrim.
 
I suppose it could be the new video card or drivers (368.69), but there has been no evidence of graphic corruption...the new card runs great...(coming from 970 SLI).

System specs: Win7, i7 2600k @ 4.4Mhz...8GB DDR3 , EVGA SC 1080 (previously 2 MSI Gold Ed 970s), Corsair 850W PS, Cooler Master HAFX case , WD 500GB Black

In an effort to stress the 1080, I let the Heaven benchmark run for over an hour at 1080 res, Extreme profile (my desktop res is 1440). Afterburner showed 99% GPU usage and the temp never went above 63C (ambient was 82F). 
Again, no issues. My CPU rarely breaks mid-50s C. during gameplay

I've wondered if it could be the memory on the GTX1080...maybe once VRAM utilization gets to a certain point it causes a CTD, but I can't find a program that specifically fills and tests all the VRAM.
Also, when it CTDs there is NO error message. Its been my experience that if the video card/driver fails; Windows give you a Video driver fail message.

I've also played Crysis 3 for several contiguous hours without issue.
I compared Afterburner graphs of Witcher 3 and Fallout 4...Witcher 3 seems to be more taxing (higher GPU usage), but Fallout 4 seems to be using a bit more VRAM.
 
If I have time this weekend, I am going to swap back to the 970s and see if the problem persists.
 
If anybody has any suggestions or guidance, I would appreciate it!
 
Thanks Mucho!

Unfortunately once you start to modify the game there is no certainty of the game's stability. There are major architectural differences between the 1080 and the 970s. I would imagine that most of the mods were made on computers running 900 series cards so that is how they were tested.
I can verify that the 1080 works fine in Fallout 4 and it is likely the modications to the game which are causing the crashes to desktop.
As a general rule of thumb, if a game is crashing to Desktop it is a game issue, if it is a TDR or full system crash then it is a card or card driver issue.
Putting a more powerful card into the system can shift the load from the card to the CPU making a previously stable CPU or RAM OC unstable when before it was fine, I have had this happen to me before.

EVGATech_RayH
  I understand that my post was long and you may have missed it:  the current install of Fallout 4 is un-modded.  
I appreciate your attention and your advice, but I do not understand how upgrading to a slightly more powerful (but less power hungry than my dual 970's) video card would "shift the load from the card to the CPU making a previously stable CPU or RAM OC unstable".  I've been building my own computers (all OC'd) and upgrading video cards for 15+ years and I've never experienced this issue, nor read of this type of issue.
As to your statement that you can verify that a GTX 1080 can run Fallout 4 without issue, I do not contend this...there are probably 10's of thousands of 1080's that run it without issue, my concern is that "my" 1080 may be having issues and I want to determine if it is in fact the new card or Bethesda's recently patched game.
 
I had hoped to have had the time today to re-install my 970's and see how Fallout 4 played, but in the high heat; kayaking seemed a more enjoyable endeavor.
Hopefully tomorrow!
 

...any other opinions or suggestions from anyone?

If you're are overclocking the CPU and/or have higher than spec RAM (DDR3 1600, DDR4 2133), then set the BIOS to optimal defaults to clear any overclocking.
 
Test again to see if the crash still happens.
 
If crashing still occurs then try the steps outlined here: http://forums.evga.com/Basic-troubleshooting-steps-Windows-clean-boot-clean-driver-install-debug-mode-etc-m2504606.aspx 

My 1080 FTW crashes once or twice when starting the game. Then it works (kinda). I get weird GPU utilization where the GPU usage drops really low without an explanation--it drops at weird spots that are not even demanding scenes. I recall this issue with my 780 during a driver update, but I solved it. The problem recurred with my new 1080, but it is much worse, as I got into spots where the fps went as low as 35fps (even the 780 didn't drop that low in that particular spot).
 
I suggest filing (bombarding) Bethesda's support team, if they have such a thing lol. Fallout 4 is the biggest AAA mess right now; I spent hours updating and stabilizing it last week and then I had that dreaded driver crash issue. I get a new powerful card, and I get another problem.  I have to contact Nvidia and Bethesda regarding the problem; people pointed fingers at my CPU but that is not the case as the 780 was doing fine with the same specs (4.4 GHz CPU that is barely at 40% usage). 

If you play different games which put equally strong demand on the video card and those games play OK then I would tend to believe that it is a game issue if that is the only game which has the issues you mention.

Good Evening to All!
 
  First I want to thank everyone that has taken the time to post in my thread!  
My troubleshooting efforts up to this evening lead me to believe it is the GTX1080 that has been causing the CTDs.  
I finally got around to  re-installing my 970 SLI setup and I just finished playing ~45mins of Fallout 4 with the same settings (2560x1440 Ultra) with no CTDs.
I invoked in-game God-mode so that I could really stir things up in the game and really push my system and there were no hiccups at all.  
With the 1080 I could, at most, play ~ 20 mins without a CTD if nothing much was happening in-game.  If there was a large battle going on, it would typically CTD pretty quickly.
So apparently there is something about the Fallout 4 Engine that my 1080 has issues with...on my computer.  
I'm pretty convinced that the issue is centered around the cards VRAM as of the games that I currently have installed; Fallout 4 seems to use the most VRAM and it's the only game or Benchmark that
has had issues.
According to Guru3D:  the calculated TDP for a GTX1080 is ~184Ws....970SLI is ~326W.  So, power wise, the GTX 1080 should be less of a power strain on my system.
Yes...my CPU is OC'd and has been since the first week of install, and has never shown any signs of failure or instability and I seriously doubt that it is an issue.  
Also, lets be honest: the GTX1080 is really only about 30% faster than the 970SLI setup (which is about same performance of a GTX980Ti).  Its main selling point for me was getting away from SLI and the obvious advantages of the VRAM increase as I play at 1440.
Before starting the RMA process, I will continue testing and then re-install the 1080 with another DDU driver un-install/install.
If you find my logic flawed, I am open to ideas.
 
 

Thumper1958
Good Evening to All!
 
  First I want to thank everyone that has taken the time to post in my thread!  
My troubleshooting efforts up to this evening lead me to believe it is the GTX1080 that has been causing the CTDs.  
I finally got around to  re-installing my 970 SLI setup and I just finished playing ~45mins of Fallout 4 with the same settings (2560x1440 Ultra) with no CTDs.
I invoked in-game God-mode so that I could really stir things up in the game and really push my system and there were no hiccups at all.  
With the 1080 I could, at most, play ~ 20 mins without a CTD if nothing much was happening in-game.  If there was a large battle going on, it would typically CTD pretty quickly.
So apparently there is something about the Fallout 4 Engine that my 1080 has issues with...on my computer.  
I'm pretty convinced that the issue is centered around the cards VRAM as of the games that I currently have installed; Fallout 4 seems to use the most VRAM and it's the only game or Benchmark that
has had issues.
According to Guru3D:  the calculated TDP for a GTX1080 is ~184Ws....970SLI is ~326W.  So, power wise, the GTX 1080 should be less of a power stain on my system.
Yes...my CPU is OC'd and has been since the first week of install, and has never shown any signs of failure or instability and I seriously doubt that it is an issue.  
Also, lets be honest: the GTX1080 is really only about 30% faster than the 970SLI setup (which is about same performance of a GTX980Ti).  Its main selling point for me was getting away from SLI and the obvious advantages of the VRAM increase as I play at 1440.
Before starting the RMA process, I will continue testing and then re-install the 1080 with another DDU driver un-install/install.
If you find my logic flawed, I am open to ideas.
 
 

One way to test out your vram theory is, using Precision or MSI Afterburner to reduce your memory clocks. You could also do that same regarding the GPU core clocks to see if that resolves the CTD or increases the time in between crashes.

Thumper1958
Yes...my CPU is OC'd and has been since the first week of install, and has never shown any signs of failure or instability and I seriously doubt that it is an issue.  

The overclock could be causing the problem. Try at stock just to be sure.