I played a good 29 hours of Fo3 (GOTY from Steam). After that I had the classic, well-documented crash-to-desktop syndrome while trying to do just about anything in the world, like bringing up the Pipboy, bringing up VATS, having missiles launched at me, you name it. I trawled the forums for almost as long as I'd already played the game. I tried the ffdshow nonsense, I tried the audio driver nonsense, I tried the whole reinstalling Windows rigmarole - absolutely none of it worked.
Well, one of the things I eventually realised after much fiddling was that all of these crashes were graphics-intensive. No CPU spike - but if I had a GPU monitor on the other hand, it would definitely have spiked. So my next thought was - let's turn down the ol' graphics settings in the Fo3 launcher. Still major graphical spikes even on lowest setting, although the crashes stopped.
The answer? Well, for you ATI people out there I would imagine you have similar options somewhere - unfortunately I've only ever used nVidia. Now, most serious gamers tinker with their graphics settings - in this case the nVidia Control Panel. Setting all sorts of things to force your graphics card to override application/game settings. And that's where the problem lies. Fo3 does a HUGE amount of background loading and data manipulation. Unfortunately poor old nVidia software overriding the in-game settings can't seem to keep up for a lot of us, even those on decent rigs.
Now when my Fo3 started crashing, I hadn't updated the driver or changed the settings - they were there from before. So the cause of the crashing is still contentious. Nevertheless, if you restore the 'Global Settings' under the 'Manage 3D Settings' section of your nVidia Control Panel (again, I'm sure there must be an ATI equivalent), you should hopefully find your game will now work, and very smoothly indeed. So to recap:
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SOLUTION
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1. Open your nVidia Control Panel (or ATI equivalent)
2. Go to 'Manage 3D Settings'
3. Go to 'Global Settings' tab
4. Hit the 'Restore' button
5. Run game and have fun!
Let me know how you get on - good luck to those still with problems!