So, is there any fundamental reason to why this game doesn't work on Windows 7?

Tried it with two machines and ALL the searchable fixes out there but still can't get it running.

Sure, some of you may get it running, but it must be something fundamental which causes this behavior in the first place.

On my 2 machines the game crashes as soon as you double click the .exe

Seriously, there's gotta be something wrong that I'm missing out on here

Yes, the fundamental reason is the UAC

Did you follow these instructions or something else?

http://www.gamesas.com/topic/1465357-installing-fallout-3-with-windows-78-and-xp/

Because the above works 99% of the time.