SPIDER-MAN

Six arms were nothing. In the 'Changes' arc, Spectacular Spider-Man vol. 2 #15–#20 (2004) by Paul Jenkins, the villain the Queen (Ana Soria) plants a kiss on a captured Spider-Man — and injects a mutagen. Peter grows extra segmented eyes, loses his grip on his own mind, and transforms, stage by stage, into a monstrous man-spider and then a full giant spider.

Then the giant spider died — giving birth to Peter Parker. A human Peter emerged from the spider's body, reborn with upgrades the bite never gave him: organic webbing produced by his own wrists (no more web-shooters or fluid bills), spinnerets, stingers in later stories' lineage, and a sharpened rapport with actual spiders and insects through his spider-sense.

The arc ran as an Avengers Disassembled tie-in, which is partly why it vanished from memory: the Avengers were falling apart in the next book over. But its changes stuck for years — the organic web-shooters carried straight into the Sam Raimi-era comics status quo, and 'the time Spider-Man gave birth to himself' remains the single weirdest sentence in Peter Parker's medical history that is entirely canonical.