The Amazing Spider-Man (1963)

The Amazing Spider-Man #50 (July 1967, the date printed on the cover), cover by John Romita Sr. "Spider-Man No More!" Peter Parker trudges toward the reader with his head down while a giant, ghostly Spider-Man looms behind him against a blaze of red, so the man and the mask he is walking away from share one frame. Swap in any hero and the cover instantly says "I quit," which is why it has been called the most imitated cover in the whole series. It is often named with Action Comics #1 and Amazing Fantasy #15 as the most homaged covers there are, and the movies have borrowed the moment as well.