Another major change is that the character of Carol Peletier has been completely reimagined (in the show she's grown into a courageous badass; in the comic she gets lonely and commits suicide at the prison), causing Kirkman to say that the new Carol is "one of the best parts in the show." That is, better than most of the parts that are actually faithful to his work.
But his favorite change of all is Daryl, who is absolutely nowhere to be found in any of the billion-something pages of the comic series. He's not even hinted at or alluded to. Hell, he wasn't even in the original script. After Reedus auditioned to play Merle, the angry racist who was ultimately played by perpetually intimidating character actor Michael Rooker, series creator Frank Darabont was so impressed with him that it wasn't even enough to give Reedus a role, he decided to create an entirely new character specifically for Reedus to play. Thus was born Merle's brother, Daryl.
Merle's role was reduced, but he still came back to lend a hand.
Kirkman is every bit as in love with the scruffy, inexplicably motorcycle-riding hero as the show's fans, and has gone on record saying that he'll never bring Daryl into the comic because it would do a disservice to the show. Meanwhile ...