The movie actually stayed pretty true to the humor and central idea of the comic. I say "central idea" because their are 6 volumes and they all have at least 200 pages in them. So obviously they couldn't go into every little detail. :P
I saw the movie three times in the theatres already. Was possibly the most fun movie of the summer. A lot of the films, (including Toy Story 3) were very suspenseful and a bit melancholy in comparison.
My gripe was if you're not a SNES /Anime fan you might not accept or understand the film and not enjoy it for what it was. They started taking the film out of certain theatres because it did poorly in the box office (despite the great reviews it received).
I also LOVE the SNES references:
Sex Bob-ombs (Mario enemy Bob-omb)
Clash of the Demon Head (SNES video game)
Crash and the Boys (SNES video game)
A lot of Zelda sound bits
The portal Ramona uses in Scott's head is the exact same portal used in Super Mario 2.
And the Final Fantasy 2 (which I think was legitimately FF 4, but back then FF 4 was FF2) song Scott played.