The problem is, how much realism do we want to kill for practicality? If you want to keep the game entirely real, then you could do real-time travel between towns. Yeah, my account payment will have timed out after the half a month it takes to cross the wastes.
Alternatively, a sort of teleportation system could fit in, and in some cases people don't even notice how unreal this is. The idea was to have a directory of towns, locations and bases and you could click one to go there automatically. Doesn't sound really Fallout themed to me, but it could be fun.
One other thing is that each of these different locations could be run by differant people, so you wouldn't have one large group of people making every new quest and plot line in the game. And there would have to be quests, whether built into the game itself or user created.
A multiplayer version of Fallout could offer us a chance to explore areas of the game which could not so easily be done in single player. Liking working for one organisation against another, the levels of power constantly shifting. It would take a hell of a lot of work (though I don't really know anything about programming.)
The game would probably allow for you to take up countless proffesions other than adventurer. You could be a Doctor (selling medical supplies as they do) and providing treatment in exchange for money. Or a guard protecting the town from raiders. Perhaps you would like to work as a caravan guard, going on regular runs about the world.
Of course, you would get countless people with silly names that kill realism even more. How to prevent that problem, I don't know. It would be nice is only Fallout enthusiasts got in, but how could that be done without killing off the game financially.
Would this kill off the setting of Fallout as we know it? I don't think so, I like the idea of the game constantly changing and expanding into new areas, but not all would agree with me.
"If we cannot live proudly, we die so!"
-Eladamri, Lord of Leaves