Last year I played Fallout 3 for several months on an AMD Windows 7 32-bit system w/ a 4 core CPU with many mods and had only the "normal" amount of game freezes (every 2-6 hours or so). I recently built an Intel system w/ an i7 2600K CPU (also 4 core) running Windows 7 64-bit. I just finished installing Fallout 3 for a replay, loaded up a saved game and bam, instant freeze every time I tried to run it. I started a saved game w/ a character in Megaton, headed out into the wastes and got about 100 yards before it locks up and I have to use task manager to shut the game down. So tried starting a new game to eliminate the possibility of a corrupted save (keep in mind that this is a fresh install of GOTY w/all DLC but no mods). I let the cinematics play out. When it got to the birth scene... freeze. I again tried older saves that had been run with mods installed. Again, 20 seconds of game play and then freeze.
First I tried the .ini mods to no avail. Same exact freeze ups. FInally I remembered a fix that I recently applied to Windows 7 startup to keep Mass Effect 3 from stuttering, only I reversed the logic. The ME3 fix required setting the number of cores in the startup configuration to more than two. Apparently Windows 7 64-bit install defaults to 2 cores. So I used the MSConfig.exe utility to set the number of cores to 4 and then ME3 ran like a well-oiled machine.
Today I read a few posts that suggested that Fallout 3 chokes on new 4+ core CPU's (i3, i5, i7). So I figured, why not set the number of cores back to 2 and see what happens? Unfortunately, the MSConfig utility won't allow you to make the number bigger, only smaller, after the first change. So I Googled up a method to reset the cores back to 2. After a reboot with the core count at 2, I fired up Fallout 3 and loaded the same old save file that froze up every time before. I proceeded to play it for about four hours without a glitch, burp, hiccup or stutter. Better than on my old PC, in fact.
As an afterthought, I never went back to restore the two ineffective .ini file changes I had made earlier, so I have no idea if these also contributed to the happy ending. Again, this was a pure install of the game; no mods whatsoever.