Four specific steps are needed to fully enjoy the game:

1. Set OffscreenRenderingMode to fbo in the registry (see http://wiki.winehq.org/UsefulRegistryKeys  ) or the game crashes immediately.
   
2. On multi-core machines you need a special bash script to launch the game with a cpu affinity (keeping it on one core) so it doesn't corrupt itself (or crash) after about 30 minutes.
3. In the TitanQuest and ImmortalThrone directories rename the Videos directory to something like Videos-dontplay, this avoids the lengthy and (at least in wine) unskippable intro videos on every launch (note: the videos are unskippable for some people on Windows as well).
   
4. Texture Quality must be set to low or you get missing parts of decorative models (seems to be missing mipmap uploads, since alpha test is on for everything in this game the missing mipmaps simply result in invisible geometry where the mipmap transitions occur near the camera).

The game runs about half the speed it does on my equivalent windows gaming machine (Athlon 64 X2 2.2ghz and GF8800GT), but is playable.

Multiplayer does not seem to work (a major disappointment as the multiplayer is possibly the best part of the game.

Here is the contents of ~/bin/TQIT on my machine:

I'd just like to thank Everyone for there work in Providing Quality feedback for,
Titan Quest and the Expansion, Without you this AppDB whuld be useless.