I am having a very similar problem with the game Skyrim. It worked great in Ubuntu 11.10 x64, but since doing a fresh system install of 12.04 x64 and reinstalling Skyrim the mouse pointer is unusable in the Skyrim program. It has done this since wine-1.4-rc1 was released for x64 and still now up to 1.4-rc5. The most extreme issue is that moving the mouse too far left/right/up/down (to turn viewpoint in game) makes the pointer appear outside the window. But also the mouse pointer seems to drift, if you like, after very small movements. It is like the mouse pointer is drunk! X.Org X Server 1.11.3 wine-1.4-rc5 Linux 3.2.0-17-generic #27-Ubuntu SMP Fri Feb 24 15:37:36 UTC 2012 x86_64 x86_64 x86_64 GNU/Linux nvidia driver 295.20
