These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
The arc about Aron and Beth visiting a nudist colony received this reaction. As did the arc that should have been at most two or three jokes about government overregulation and the drug market. It seems the webcomic will inevitably undergo this every now and then.
Base Breaker: Audrey has become one, to an extent. She is generally seen as either a decent and likeable character, or as a faulty and problematic portrayal of transgendered people. Naylor later described those who criticized her portrayal as suffering from "Audrey Syndrome".
Ensemble Darkhorse: Charlie. It's gotten to the point where the Hatedom fears for Charlie every time she shows up in the strip because they don't want to see "the last likeable character in the strip" get ruined.
Also, Angelica. Usually treated as the villain of the piece, the strip's detractors look on her as something akin to a hero as she's one of the few characters that isn't a complete asshole.
Despite her Base Breaker status, Audrey. It helps that she's legitimately cute and sweet, and she was part of one of the better story arcs.
Family-Unfriendly Aesop: The infamous "muffin arc" goes into great detail about just what a hero is supposed to be. The comic asserts that a hero is someone who does a job for money, and does not do more than is required of them by that job or their pay, and that in fact trying to help people out of a sense of moral obligation or selflessness is unheroic, bordering on villainous. Not to mention the moral that if someone tries to be a hero for entirely selfless reasons, people will instantly take advantage of him or her and use them. (It's basically, Atlas Shrugged as applied to furry superheroes.) Of course, this all ties in with Naylor's Objectivist views.
Les Yay: Charlie is very attracted to Janie and ultimately gets her chance to kiss Janie for real (while dressed as a boy). Janie lets her down easy, saying she would not want to hurt Charlie as a friend. Although Janie is shown licking her lips appreciatively at the arc's end.
While drunk, Trixie (somewhat humorously) tells Beth "If you were a man, I'd totally lick your pussy". Later on, they have sex (naturally expanded on in one of Naylor's adult comics, called "Straight Girls Kissing in the Shower") and Beth promises to visit her when she returns.
Revisited again and invoked in the story arc where Aron attempts to get close to his latest crush Audrey, who is involved with a Butch Lesbian. To sneak into a lesbian convention the two are attending, Aron disguises himself as a woman, and Trixie pretends to be "her" girlfriend. Aron manages to kiss Audrey...only for this to seemingly become Ho Yay when "she" gets a boner. However, Audrey is then confirmed to be transgender, and she and Aron develop a sweet relationship following the obligatory awkward humor that ensues.
Strawman Has a Point: The small girl Angelica was created as a strawman into which Naylor stuffed everything he hated, from politics to spirituality to musical taste. She's also widely considered the most likeable and sympathetic character in the strip since she seems to be one of the few characters that doesn't act like a complete Jerkass to everyone around her. For five months, she's been waging a campaign against the strip's Objectivist protagonists, and most reader reaction is rooting for her.
Toy Ship: Thomas and Miko hint at this in one strip when they practice kissing. Janie later teases Thomas when Miko's Education Mama gets her a tutor and notes how she's spending her time with him instead of Thomas. Of course, Thomas himself adds to it when he worriedly asks Abigail for something that would help make Miko uninterested in the other guy. Eventually, Miko admits that she's already attracted to Thomas, especially because her mother hates him.
What an Idiot: Fisk, Elizabeth, and some other adults end up stuck in a tree with a bear circling the ground below. Elizabeth gets one bar on her cell but ends up blowing any opportunity to call for help by fawning over pictures sent by Trixie of their kids.