I would very much like to know what kind of Tweak you did
Ok, but make sure you've got a backup of your OS incase anything happens as I won't be held responsible even though this is normally ok to do if you follow what I've typed.. so only do so if your very comfortable.
Only apply this if you have SP1 in Vista, without SP1 you will encounter serious problems. Restart your PC after applying this changes.
Open RegEdit and go to: HKEY_LOCAL_MACHINE \ SYSTEM \ CurrentControlSet \ Control \ Session Manager \ Memory Management
Change the value on PagedPoolSize to 18000000 (hexadecimal) from the default of 0. For other systems, change CurrentControlSet to look for ControlSet00x X = where CurrentControlSet is located.
This isn't the setting for PageFile which is related to how much RAM you have. More info on this can be found here: Link
Also, if you have X-Fi soundcard, use Alchemy and enter the following correct sound config as audio can be the main cause of app crashes - so don't have lots of codecs installed or make them as an exception:
Game Title: Fallout 3
Registry Path (this is for 64bit Vista in bold): HKEY_LOCAL_MACHINE\SOFTWARE\Wow6432Node\Bethesda Softworks\Fallout3\Installed Path
Settings
Buffers: 6
Duration: 5
Maximum Voice Count: 128
If you still experience crashes, either load one of your previous saves or completely remove your mods using the excellent Fallout Mod Manager. I recommend this even if your mod states it is compatible with the latest version. Once its stable, don't revert back to using mods if you can help it.