I'm not a frequent movie-goer and don't watch a lot of TV/DVDs or do much DVR-ing, so I've only seen 52 of the ones on the AFI list.
The biggest miss for me, as for a few others, is Citizen Kane. But that does happen to be one that I've got on DVR right now, so I will be watching it sometime soon.
I'd like to put in a word to heyabbott for Schindler's List. It's an affecting movie without being overly horrible, if that's makes sense. I found it actually kind of understated, in an effective way. Maybe that's because it's in black-and-white, but I found it one of the more watchable movies about the horrors of the Holocaust, and it was well worth seeing.
Flip Wilson, even for a relative non-movie enthusiast, that's quite a list of ones you haven't seen. Kind of surprising.
And, these are just opinions, but here goes: I generally love science fiction, but 2001: A Space Odyssey was one of the most boring movies I've ever seen. I also hated Network.