If there's a prequel, I'd much rather have one almost immediately after the bombs dropped. Think of Randall Carter from Honest Hearts and imagine you're playing somebody like him.
It wouldn't necessarily be core region, but a lot of the basic Fallout and Bethesdian assumptions of the gameworld work better when the Great War is still a fresh reality. Stuff like cans of beans, raiders and radiation become realistic concerns and not just wallpaper. And it's fair to assume that most raiders would actually have believable motivations because they're just doing what you're trying to do: Survive.
I'm also going to go with the school of thought that New Vegas mostly accomplished a lot of the stuff Van Buren did. (And seriously, yet another genocidal megalomaniac for a villain? Yawn.)