The E3 presentation showed us a lot of nice things about Fallout 4, but not everything. There are two things in particular that I'd really like to see at some point, whether in the main game, added by DLC or (in the first case) added by a sufficiently stable mod).

1. Something that is both mobile and can fulfill the basic job of a player house i.e. somewhere to put my loot. My go-to example would be an atomic car like the Highwayman in Fallout 2. Even if it can't go everywhere, being able to load the boot with guns and go on a postapocalyptic road trip across the map with my companion and my dog would be fun. Or if that's too hard, it could just be something like a boat that can be transferred between a few safe ports via a menu at the helm.

2. At least a few really well fleshed out companions. Bethesda's made some good progress in this regard with Serana in the Dawnguard DLC for Skyrim, as have New Vegas and various companion mods. I hope that the game has some options for companions that through AI and dialogue feel like people.

2a. Letting us be accompanied by two humanoid companions by default and not just one would be nice. Hearing Serana give her two cents about the places you visit was fun and having interactions between companions, even if it's only once in a blue moon like the elevator conversations in Mass Effect, could be fun too.