I've got an ASUS Rampage V Extreme, with an Intel 5930K running at 4.2 ghz, twin EVGA GTX 980 Superclocked cards running at stock settings, 16 gig of GSkill Ripjaws F4 DDR4 2666 running at stock timings and voltage, a CoolerMaster 1000 watt PS and an Antec Kuhler 920 H2O CPU cooler all in a CoolerMaster HAF 932 case with plenty of air flow.  The OS is Windows 8.1 pro, fully updated, loaded on a Samsung 250 gig 850 Pro SSD.  CPU normally runs at about 33-35 deg.C in the summer.  Video cards are also running at about the same temp.
 
When I first boot it up, it runs fine.  If I run Futuremark 3DMark Firestrike Ultra, I get a cumulative score of about 6300, which I think is about normal for the setup I have.
 
After the computer runs for a couple of hours, even sitting idle, if I start up Firestrike Ultra, it takes forever to load and run, and the score is down around 2300!
 
One doesn't notice too much else except that programs seem to take a bit longer to load and start.  
 
I've run all the diagnostic programs I have and scanning for any malware never turns up anything except a few tracking cookies.  I've run Spybot, Malwarebytes Anti-Malware and Windows built-in anti-virus.
 
I just can't seem to find anything wrong, except it slows down over time.  Running Task Manager shows no undue disk activity and no unusual activity on the network or large loads on the memory or any service running more than 1% or anything like that.
 
Any suggestions would be appreciated!  I'm about ready to just do a complete re-install except I'm dreading the time it will take to get everything back loaded and running.

Check your Task Manager to see how much free memory you have. These latest drivers from nVidia are getting a lot of complaints about memory leaks. Try an older driver to check.

I'm sorry to bring this thread back from the dead, but I'm having the exact same issue with my PC, on almost the same config: Asus Rampage V Extreme, Core i7 5930K, dual EVGA Titan X SC cards, 32GBs of G-Skill Ripjaws, 256GBs Samsung 850 Pro SSD, and EVGA G2 1300W PSU.
 
My computer has the exact behavior, works fine as long as I'm using it but if for some reason I stop using it for a while it becomes super slow, I open the task manager and the CPU speed is locked at 0.39GHz! This is on Win10 Pro 64bit. Were you able to find out the root of your problems?
 
I've tried everything, disabling speed step, locking my CPU at 4.5GHz on all cores with no turbo boost, formating my OS, and I still have the same issue, I know for a fact it's not temp related as both the CPU and video cards are on two separate water cooling loops and the temps never go higher than 55 degrees.
 
Please let me know if you were able to solve this issue, it's tormented me from day one (I got this rig on the day Haswell-E became available), and I'm tired of having to reboot my PC every time this happens! :(