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 1989 and was kept in.