Lots of people (including myself) have had a terrible time getting this game to run well with vsync enabled. After some research I have found a somewhat effective fix for nVidia users. I thought I'd share this since it's quite a common problem. I currently use a GTX 560 Ti with drivers 305.53.
In Darksiders II Options: --Set Vsync to "off" --Set Full Screen to "off"
In Nvidia Control Panel: --Set Vsync to “Use 3D applications setting” --Set Triple Buffering to “on”
D3D Overrider: --Set V-sync to “on” --Set Triple Buffering to “Off”
(Note: for D3D Overrider, download RivaTuner here: http://www.guru3d.com/content_page/rivatuner.html. Install RivaTuner, copy the D3DOverrider folder to your desktop, then feel free to uninstall RivaTuner.)
For full screen playing: If you want to play full screen, just download the "Windowed Borderless Gaming" application, which lets you play in windowed mode, but with the full screen.
M4A78T-E | AMD Phenom II X4 955 Processor 3.21 GHz | 16 GB DDR3 (4 x 4GB) RAM | GeForce GTX 560 Ti 1024 MB
I'll have to try this out. I've had DS2 since it came out and it's ran perfectly smooth on max settings. I haven't played it since September and when I tried playing today it just started running like s***. Nothing I've tried has fixed the inexplicable slowdown. Hopefully this stuff works.