I was thinking ...
If you started Fallout 3 near a few places from 2, that you could pull off a plausible story off, or excuse of some kind to be blunt, then you could start the game say in the remains of Vault city and Gecko N.P.
The NCR no longer exist , something wiped out Chi in the San Fran, or they disappeared suddenly.
From then on you find yourself drawn somehow into final destruction of Gecko and Vault city and you flee with refugees into new territories.And i would make it so that you are one of the ones responsible for it , unwillingly but responsible.
than you could decide what to do about it.
Survival, traveling alone or with the others, fighting for yourself or for something else, protecting the rest of refugees or not...and so on....until you stumble into new locations.
Thats a simple example, without many details.
You could prolong the players stay there and give him few opportunities to visit a few more locations or find out about the past. It all depends how much connectivity you want, and how many details you put into that kind of beginning.
But maybe it could be pulled off in a smaller amount. And to use it as a story instigator not just as a dead weight.