No one has spent more time and effort into The Walking Dead than Robert Kirkman, who created the comic series and has been a big part of its expansion on television (among other forms of media). Obviously coming up with a top moment would be a rough one, but when asked about his favorite issue of the comics, he did come up with an answer, and it's one that indeed became one of the more memorable episodes of the show.
I guess if I had to pick one favorite moment in the story, it's probably issue 50 where Carl and Rick are alone after the prison attack, and Rick is seemingly dying, and it's just an entire issue of Carl trying to survive on his own, and thinking he can't survive on his own until realizing that he really can. That was a fun story and a big turning point for Carl, and I actually got to write that episode in the show, so that was a lot of fun too. Thinking back, maybe I'd pick that one.
The issue he's referring to in this interview from EW's The Ultimate Guide to The Walking Dead was indeed a departure from anything that The Walking Dead had delivered to that point, with Rick and Carl as the only main characters seen in the issue. Similarly, the TV episode that Robert Kirkman penned, titled "After," whittled out all of the characters except for Rick, Carl and Michonne, which was a pretty big choice for a midseason premiere. It's easy to see why it stands out in Kirkman's mind. (Plus, it jumpstarted all things Richonne.)
Both the comic issue and the episode add some angst-ridden depth to Carl Grimes, which helped to pull him out of the "just a kid" labeling. It helps if you look at The Walking Dead as an origin story for Future Carl - his comic narrative makes that concept a lot more interesting than the live-action version - with this being the character's first big move towards independence. Before this moment, Carl couldn't have been a badass with a missing eye, but after this, he earns his hardcore reaction to it.
Plus, Issue 50 was the halfway point to getting to Negan, and the story beats kind of mirror each other. This moment was Carl telling Rick that he was no longer in charge of the younger Grimes' survival, and #100 was Negan telling Rick that he was no longer in charge of anything. Not the most direct reflection, mind you, but it fits.
Walking Dead fans might recall this particular episode was the impetus for the hilarious Bad Lip Reading music video "Carl Poppa," which has once again become this week's earworm.