I found this out back when Operation:Flashpoint came out, I was using Rage "3DTweak" and one other (can't remember) and everytime I tried to load up the game, it would crash, as well as a couple other games I had at the time. Since then, I've never used these tweaking programs. I also don't get into these virtual drives, and other 3rd party stuff, so maybe try this. I occasionaly get this "popping" static noise in SH3 that others are getting, and I had the same problem with Half Life 2 - and this was fixed with a patch from Valve (at least for me). Others seem to have issues still, and I wonder if its due to these tweaking programs.
Athlon 3000+ overclocked to 2.21 ghz
1.5 gig 3200 ram
ASUS A7N8X-X with latest BIOS
Radeon 9700 Pro with Cat 5.3 (not overclocked)
DVD (of course) - just got it, don't remember brand but is a shoot off from JVC
Samsung 17" CRT Monitor
Audigy Gamer with Creative 5100 Surround system
450W power supply
I currently run the game at 1024x768 (of course), 32-bit colour, maxed out AA (6x with Temporal enabled) and AF (16x), Catalyst AI (whatever that is) on full advanced, Mip Map on max quality. All hardware full acceleration.
This game runs Excelleeeently smooth - no hiccup except for the audio popping that occurs (I expect to be patched-solved. Amazing visuals. There is a slight pause when the sub surfaces, I guess the game pauses to "POP" the crew on deck, but that's it.
Hope this helps some people.