Things I want out of Fallout 4 (and any Bethesda RPG going forward, really):
No essential NPCs.
I hate immortal NPCs with a passion. It kills immersion and it takes away player choice. If I choose to kill a character and it breaks a quest, that's my fault or my intent. The game should be smart enough to work it's way around a key character dying and it would add to replayability.
Not being reliant on a quest marker.
I want the ability to play the game from start to finish without a quest marker. I don't mean a stupid toggle in the options menu, either. If an NPC gives me a quest, I should have all the information necessary to complete it (or take steps to completing it) without needing a quest marker. So pointless, empty dialog like "Talk to Bill in Port Wellington." won't do because it tells you jack shit. How about, "Talk to Bill in Port Wellington. If his out-of-control beard doesn't give him away the alcohol on his breath will." Now I'll have an idea of what he looks like and where he'll probably be, but I'll still have to search for him myself instead of following an arrow.
Diverse, complex quests.
Skyrim hooked me on the Bethesda formula but going backwards and playing Oblivion made me realize how dumbed down Skyrim's quest structure was. Going back further to Morrowind made it look even worse. I want Bethesda to return to form on this.
And yeah, those are the big ones.