Is it possible to control graphical setting outside of R3E? I tried the NVIDIA control panel and NVIDIA Inspector and nothing seems to affect R3E (mss32.exe and RRRE.exe used). As a quick test, I even enabled VSYNC in the Global Settings of the control panel but this doesn't affect R3E.
I remember a post from @Fairman where he discribed some graphic-Settings. So it seems to have an effect usually. Are you still running on Win8.1 or have you done the update already?
I'm on Windows 10. I'm not really having any problems but thought I would try a few settings through NVIDIA Inspector but nothing seems to work - nothing affects R3E. And as I mentioned, I set VSYNC in the Global Settings of the NVIDIA control panel to see if I can affect R3E. I had VSYNC off in R3E but enabling in Global Settings does to affect R3E - still no VSYNC. Its as though R3E overrides any NVIDIA control panel setting.
I use in game vsync and Nvidia Inspector fps limiter to 60. This is butter smooth for me without a hint of stutter. I also use RiverTuner's fps limiter for some games but just not for R3E as I see very occasional stutter with it. I am also on Windows 10 but with a Titan X and Skylake i7 6700k at 1080p