Wide, open world; Great variety; Play however you want!
Things are a lot different now, as expected. This is the best in the series with all the bells and whistles of a modern RPG. The pedigree feels a lot like Oblivion, but the setting and story is so unique that it plays a whole lot differently from that other classic -- and that's a good thing.
While the graphics are not quite up to par with other similar marquee games, everything else is done in such a way that the game stands out in a crowd. From the music to the "look" to the stories to the combat, everything feels uniquely "Fallout" -- sort of creepy, very addicting and tons of fun to play.
Decision making plays a big role, as you're allowed to approach different situations in a different way. None of your decisions result in game-ending situations, but most of them result in different branches --- allowing you to carve out your own story as you wish. In fact, there are several alternate endings depending on the choices you make. This is a true RPG, and one that should stand the test of time.
If there's anything I didn't like about the game, its the fact that some quests seem too complicated and not interesting enough (like the Nuka-Cola Challenge and the Survival Guide), but in the end these are just minor annoyances to what would otherwise be a masterpiece.