Lex Luthor was originally drawn with red hair, but was abruptly changed to bald after an artistic mistake by illustrator Leo Nowak. Not only has it stuck with Luthor's popular image ever since, but was indirectly responsible for Luthor taking the Ultra-Humanite's place as Supes' arch nemesis as DC didn't want two bald mad scientists battling Superman (and thus Ultra-Humanite gained his trademark tendency to Body Surf and was Put on a Bus for several decades).
During one arc of Invincible, Omni-Man marries an insect-like alien, and there's a panel of him kissing her and Invincible looking disgusted. According to the sketchbook in the back, the artist made this as a joke and Robert Kirkman decided to keep it in the actual issue.
Wolverine's iconic mask was due to this trope - when he joined the X-Men in Giant-Size X-Men #1, he was meant to keep the same mask design that he had when he first appeared in Incredible Hulk #181. However, the person who drew it, made the ears and eyes too wide. However, when it was shown, they thought that it made him look like Batman and was kept in.
In the script for an issue of Aquaman: The Atlantis Chronicles, Peter David described the "face" of the meteor that destroyed Atlantis. He meant it metaphorically, but the artist, working from a script translated into Spanish, took him literally and drew the meteor with a skull face on it. When he saw the art, David said "Keep it," reasoning that the only thing more terrifying than a meteor heading right for you is a meteor heading right for you WITH A SKULL ON IT.
In Il Papero del Mistero ("The Duck of Mystery") Scrooge sets himself and his relatives to make a soap opera, and specifically tells everyone that he won't give them any script, only character names, initial roles and a scenario and then they'll have to improvise. Cue such gems as an episode where everyone but Scrooge's character get poisoned by the others (in two occasions by accident, because Gus' character stole a slice from a previously poisoned cake and the nephews' characters made Grandma Duck's character taste their attempt at the formula of a Coca Cola Expy and Grandma Duck decided they failed), Donald faking an Alien Invasion episode when the other actors go on strike, and Jubal Pomp photobombing his way in the story with attempts on Scrooge's life (it's that kind of story).