I came across this list today, and I was thinking that it was pretty cool, as much for the titles as for the classic covers:

http://thisrecording.com/today/2010/1/18/in-which-we-count-down-the-100-greatest-science-fiction-or-f.html

But of course there's no way to put out a "comprehensive" list without people getting upset that their favorites were slighted.  And you know, while I do agree with many of the titles on this list, I also missed seeing titles like Lloyd Alexander's Prydain Chronicles, A.E. Van Vogt's Slan, Margaret Atwood's The Handmaid's Tale, and ... well ... anything by Octavia Butler, Neil Gaiman, and Jules Verne.

Still, check out the list and get some reading recommendations (and enjoy those crazy covers!)