First thing. Seriously... ZOMBIES! Or at least enemies that closely resemble zombie behavior, the game S.T.A.L.K.E.R found a way to do that without them actually being "zombies", but close enough to give you the zombie experience. Fallout 1 and 2 had some enemies that somewhat resembled zombies, but I felt like they weren't close enough. I really yearned for some good zombies in those games. Anyone remember those glowing guys protecting one of the vaults? I don't remember which one. I'm not saying they actually have to BE zombies, but something that closely resembles them.
Also, TONS areas to explore that aren't related to quests. Abandoned ruins and buildings, including factories, homes, towns, cities, farms, military bases, gas stations, power stations, tunnels, bus stations, airports, neighborhoods, subway systems, train stations, etc. You get the idea. The more ominous the better! Please reward explorers with goodies too. Ammunition, weapons, supplies, medicine, first aid, drugs, armor, stuff you can sell, etc.
Finally non-linear open game play that lets you choose what you want to do and how to get there, with lots of possibilities.