Let's see here.
Kind of depends on when you stopped reading comics. There are some really excellent trades out there for Supes, Batman, and the JLA. Kingdom Come is really worth reading, as is Long Halloween and Dark Knight Returns. DK2 is not nearly as good as the first one; I wouldn't bother picking it up. There are some really fun JLA trades and one-shots out there as well - I'd probably pick up Tower of Babel, Earth 2, and maybe a couple of others.
In the Marvel line... hm. Ultimates is an excellent title (there are two trades for that). In general, the Ultimate Universe is really solid stuff. Ultimate X-Men and Ultimate Spidey both have a great series of TPBs for them. Strazinsky's run on Amazing Spider-Man has been consistently excellent, as I've come to expect from his stuff. Neil Gaiman's 1602 (mutants start showing up in 1602 England) is awesome, though I think it'll be a while until that comes out in TPB form. Joss Whedon's Astonishing X-Men is the best X-title out currently - the rest are a jumbled mess, IMO, and not at all worth checking out.
In the smaller-press stuff, I'd recommend Y - The Last Man and Fables, both excellent series. Powers was an excellent series for some time, though I haven't really enjoyed it recently. Read "Who Killed Retro Girl?" and "Sellouts" for a very interesting examination of how normal people would deal with super-heroes. Midnight Nation and Rising Stars are both excellent reads, though Rising Stars is intensely frustrating, since it was canceled just a few issues before the end. Still, it is good enough that it's very much worth reading. Preacher is good if you enjoy Garth Ennis's twisted nature. And, of course, you should read Neil Gaiman's Sandman if you haven't already. EVERYONE should read Sandman.
Yeah, that should be enough to get you started.
