I've had some hard-to-guess-but-always-around crashes after having modified a value in Prefs.ini by hand. I've usually tried changing GfxForceNoBump, GfxForceNoPointSprites, GfxThrottleFrameRate, and FullScreen to name a few. Sometimes when you toggle a feature, it works once, and then crashes continually each time after the splash screen. Sometimes it crashes once, then works continually after that. Changing a value so it works once, then going into the options panel in game and setting a feature (or doing nothing at all) always fixes it. That is, changing options in game always seems to work, and sets whatever was borked with the system back to normal.
The debug.err files for all the crashes were the same, see here.
Edit: Well I take some of that back. Sometimes when changing the resolution (and maybe some other features) through the game I got the same crash once, works continually afterwards syndrome as before. Gah.