Depending on your perspective, Mutant Year Zero. Technically, MYZ builds on the Swedish game Mutant from the early 80s (which in turn was a Gamma World ripoff with BRP-like rules, though MYZ uses a completely different system), but they really have very little in common other than post-apocalypse and mutants.EDIT - In fact apart from Apocalypse World, which is absolutely 100% "about those things" (talking and problem solving over fighting, particularly), and "major RPG" because of it's insane influence, has a major new post-apocalyptic RPG been published after 1990? Not an update, a new IP. Gamma World was 1978. Twilight 2000 was 1984. After The Bomb was 1986. I can't think of any major other ones. Legacy: Life Among The Ruins is lovely, but it's not major.
MYZ takes a different approach because of its intense local focus. The PCs come from an Ark, making them part of a settlement of 200 or so mutants whose society starts on the brink of collapse because their old resources are being depleted, and the Old One who previously guided and supported them is on the verge of death. Oh, and the mutants of the Ark are unable to reproduce. Adventures tend to either be about internal Ark stuff or exploring the outside world, and part of the game is deciding how to develop the Ark by building either specific places (like a pig farm to provide more food) or concepts (different forms of government are among the late-game things to "build"). PCs are built with a number of connections to other people in the Ark, and they are also bound to it because most of the surrounding area is filled with Rot (an abstraction of radioactivity as well as biochemical agents and other badness) that will accumulate if you're away too long, so you need to return to a safe area in order to get rid of it).