I would like Fallout 4 to:
1) Be made on a modern engine (screw GameBryo, we're in 2009 for crying out loud, stop milking it, please).
2) Be set in another country, perhaps the U.S.S.R or China, or somewhere (specified) in Europe, perhaps England, or Spain/France/Germany/Italy and so on, so many choices.
3) Have a larger world than Fallout 3's, something more along the lines of Cyrodiil in size, perhaps bigger, but filled with just as much as Fallout 3 already is (it's just too small for my tastes, it feels "squished" together, even in the wasteland, things too close to each others, just look at the Pip-Boy map).
4) Have multiple "main quests" rather than only one (I could explain more on that if necessary, but it ain't new to video gaming, it was seen and done before).
5) Have better, more significant consequences by choosing to be "good" or "evil", for instance having entire towns and massed populations eventually knowing about you and your actions and even chasing you as your journey progresses, and for example being extremely "good" would attract attention of bounty hunters or mercenaries (similarly to Fallout 3's Talon Company but pushed to extremes, directly affecting game-play more than just encountering a small raiding party posing no real threat).
I got a long list but I'll leave it at these five points.