I know its already been mentioned and more or less discarded, however the "run a town idea" could work if fixed up properly. Let me explain. Any of you ever played a game by the name of Breath of Fire 2? In this, you find an abandoned building (two story, but the stairs are ruined), now, as you travel, you encounter people who just arnt happy where they currently are, but have no where else to go, and you can send them to the building, which they work on and repair, then as more people show up, they build a few more houses, etc.
This might work in fallout if done properly. Maybe a hidden area, the ruins of some town or somesuch, and as you travel, youd encounter people who you could persuade to go to that town. A merchant or two, a doctor, maybe a scientist, guards, etc. Remember those slaver caravans you encountered? If you killed the raider, you could send the freed slaves to the growning town. NPC's could also be sent there, and later hired maybe. (Not all though, since Sulik for example is looking for his sister, he wouldnt sit around.) And others, such as Casidy would only go there if the town already had a doctor, and a supply for heart medication. (So youd need to persuade someone in Vault City to smuggle out medication to your town.)
Youd need guards to protect the town, who could again be hired from other places. Defending the town could get complicated, maybe every couple of months it'd get attacked by raiders, so if you dont have sufficient guards, itd be taken over. In which case youd have to go and exterminate the raiders. Any extra weapons and ammo you aquiered could also be dropped in the towns baracks, increasing your guards efficiency. If you sold all your weapons, you could have a lot of guards, but since they have no weapons they'd still be useless in repeling raiders, and so on.
So there wouldnt be much need for micro managment, just to 'collect' citizens, and supply the guards with weapons. Which would be a money drain, since instead of just selling that minigun, you might want to give it to the guards.
The ending would of course, need an extra sequence for the town, if it had the key personel (guards, doctor, etc.) it would succeed, if not...
Just a suggestion, I figure that like this it wouldnt destroy the Fallout feel as much. After all, how did Redding start out?