I have these suggestions, all at the far ends of the thematic and mechanical spectrum.
Mutant Future. If what you're looking for is an old-style, Gamma World-like game with simple rules and the ability to include wild amounts of mutants, androids, etc etc, then I suggest Mutant Future from Goblinoid Games; if you want to season it with magic and monsters, then you can sprinkle in bits of Labyrinth Lord, from Goblinoid as well. At the lower-level end, characters are certainly fragile, I suspect.
Apocalypse World. Vincent Baker's latest game is a decidedly new-style game with lots of interesting mechanical flourishes. Characters can be fragile, and while each character has some special stuff they can do, you can easily frame these gifts as within a gritty heroic scope and not post-apoc-folk-in-tights. Baker bakes in some weirdness into the game (the Psychic Maelstrom), and you can easily spice with mutants and freaky stuff without bending the game. With each game Baker publishes, he gets better at not just giving you a great game, but giving you great, clear explanation on how to play it. Apocalypse World's rules are lengthy compared to his previous efforts, and a great deal of that is in laying out, very clearly and explicitly, how you should play the game (before you inevitably attempt to hack it to suit your group's desires).
Aftermath. If what you're looking for is an old-style, gritty, simulation-y game with a deep, flexible rule system, it's hard to do better than the original. The game has a somewhat undeserved reputation as intensely difficult: I disagree. The rules are deep and complex, granted, but they're also very clearly explained and rational in approach. Additionally, FGU now sells a new "Tech" supplement for widening some tech for the game (aliens, mutants, space travel, cyper-computery stuff, some updated tech), and a "Magic" supplement if you want to inject a magical aspect to the game. Aftermath is clearly designed for deep, long-term, simulationist play, but it's fundamentally no more complex than full-on GURPS or D20.
Generic rules. You can also try using several generic rules-sets to get what you want: GURPS would work, probably, as would Greg Porter's two most recent game efforts--CORPS and EABA. In particular, EABA with the Stuff supplement (for building machines and creatures and such), and perhaps with one or two of the campaign supplements, would suit well. Porter's designs are smoothly developed, but are deep and simulation-y -- the reason I explicitly call out Aftermath over EABA or GURPS or HERO or BRP, or another generic rule engine, is that Aftermath is specifically written for post-apoc play, while being built on top of (essentially) a generic, simulationist game engine (the same that appears in Daredevils and Bushido).