Warning- Text Wall.
Just a few things. Like others have said, remove invisible walls. Period. I am perfectly fine with the "You cannot go in this direction any further" line.
Introduce rock climbing or don't have inaccessible areas show on the map. I hated being right next to new location (that's what I like to do in that game, discover locations) and having to squirrel around a rock formation.
Add a mini map. The Pip Boy is awesome, but c'mon. Even if that tech doesn't exist in game it could easily represent all the information that someone would glean if they were in the game world.
Better AI/ engine.
Being able to use cover a la Mass Effect or even Red Dead would be nice. Sans cover the game never really seemed like a shooting game to me.
Vehicles but only if you can explain them without ruining the verisimilitude. Maybe if the setting was days after the Great War it could work.
Undo the progress- as others have said things are going too well
Again backing up the timeline may help, though I would prefer the series continues forward.
A settlement creator system would be cool to. Set up your own shack. Set up a shop, gather building materials and make your own settlement! What a cool thing to do even if it didn't help you out very much.
Bigger maps, more people, more believable world economy/resource allocation.
I like the midwest/ central US idea, maybe around the great lakes. Call it Frostburn or the Frozen Wastes or some such. Nuclear winter and all that jazz.