For me, obviously hopefully they'll use the Creation engine and it'll be better than Gamebroyo. What I'd like to see is a Fallout set in the Southern California area, specifically Los Angeles. There's a lot you could do with this. I would begin in a vault again up in the mountains, and you escape and it's a little Jeremiah Johnson like at first.
However, you eventually work your way toward the coast. You could do a whole thing that riffs on the idea of classic Hollywood and have that be a motif kinda like New Vegas. I would have a bombed out Los Angeles skyline with lots of crumbling buildings, and the big final battle would take place there. I would also add in vehicles, and in the big battle for part of it you can fly one of the vertibirds as you attack downtown LA.
I'd also work the coast line in with the idea of taking ocean water and using it as drinking water. One idea I think would be very cool is to have a pier that kinda leads to a Bioshock Rapture type city, leaking but still around that goes under the water and is built along the shoreline in the sea. You could maybe have it under control of a gang that's obsessed with drugs, and one of your missions takes you there.
I would also deal with the idea of slavers and have them be a full on named group like Caesar's Legion. They would stage gladiator matches in a newly built shanty-colosseum near the beach, and depending on your choices you may end up fighting in the arena or betting on it or gaining control of it and either shutting it down or gaining profits. I would keep the reputation system and expand on it.
Like I said, some vehicles would be a nice addition. The map would be the coast to the mountains, with Los Angeles and Hollywood in the middle. I'd maybe have a casino on Pacific Coast Highway, and in the story I'd deal somewhat with the concept that the LA area is being rebuilt slowly and various groups are vying for power of what they believe "could be a fully functioning city again one day."