I installed through steam, in winecfg I set it to not do the window manager stuff (everything unchecked) and then for my registry entries, I added some borderlands.exe configuration, I don't know offhand what the defaults are on some things nowadays, but I set the following under the Direct3D key.
DirectDrawRenderer opengl
OffscreenRenderingMode fbo
RenderTargetLockMode readtex
UseGLSL disabled
The important one there is the UseGLSL disabled I think. I haven't done rigorous testing on the differences each of those makes, as I've been playing rather than testing.
Also you may want to consider MouseWarpOverride set to force, under DirectInput. Since its based off the unreal engine which apparently doesn't ask for the mouse causing it to warp properly.
Only thing is this game actually uses menus more than most FPS games, so you might not want to force the mouse warp.
Also, after further play, it seems some inside areas do cause more problems as I stated earlier, the Sledge's Safehouse area in particular has lots of texture flickering.
I suppose I could include the hardware config; mac pro 09 octo 2.26 and a GTX 285 1GB, and the GT120 is still in there as well, although its not in use, unless wine can do physx....