Astonishing 1 & 2 (or the omni) are worth getting for sure.
Rise & Fall was a lot of fun.
Supernovas is yucky. The art is nearly impossible to follow and the story could have been condensed to 2-3 issues.
Messiah Complex really seems to divide people. I held out and read the entire thing when the OHC was released... it left me in a deep depression for days. Just awful and inconsistent.
Haven't read the Manifest Destiny stuff... probably will pick it up in tpb form.
I love Inferno but honestly that's probably just due to nostalgia.
Really looking forward to Mutant Massacre... hope it holds up after all these years.

I know they aren't oversized, but for the best written, most fun (and somewhat more mature) X-title, check out the X-Factor PHCs. By far my favorite.