I quite like some of the speculation I've heard around FO4, alot of it has said it will take place in Boston and will focus around the Commonwealth. Think I remember something about the main quest possibly being about the fight between androids and the commonwealth.
Whatever the case, I hope they go for the kind of atmosphere FO3 had over FNV. I found FNV to be far too...unapocalyptic feeling, there was no where that I thought "I'd rather shit the bed than go in that building" or anything that made me feel sad or unhappy.
I also hope they don't make it like Skyrims quests. I found Skyrims quests were all very hollow and kinda like the quests came to you (Like you kind of discover them as you're doing other quests), unlike FO3 where you had to go out of your way to find them. Also too many quests that decided the fate of the land or the world or the ENTIRE UNIVERSE. (Main quest, Wolf queen, Dawnguard off the top of my head)