In an alternate timeline, the child of Mary Jane and Peter Parker grew to become "Mayday" Parker - a vivacious teenager with a talent for basketball. Her athletic prowess and bubbly personality made her a popular student with a hectic social life. May was unaware of her father's heroic past until her own latent powers revealed themselves at a crucial point in a ballgame. Walking home afterwards, she was menaced by the Green Goblin - Norman Osborn, Jr. - who hungered for revenge on Peter Parker for the long-past battle that killed Norman's grandfather and crippled Spider-Man. Instead, it was Spider-Girl who faced the new Green Goblin, and twin legacies were born anew.
Peter and Mary Jane Parker initially forbade May from adopting her new role, but they soon realized that their protests were in vain, and Peter chose to help teach his daughter the skills she would need to survive. As Spider-Girl, May encountered many new villains and allies in her war against crime. Most importantly, she convinced Norman Jr. to abandon his pointless feud, and they co-founded a loosely banded super-team of "New Warriors."
In a battle with the super-villain Killerwatt, who controlled electricity, Spider-Girl was severely shocked. This apparently caused her to lose her powers, until, in a battle with the new Spider-Man, she fell into a generator, where she was, again, shocked severely. Her powers returned, along with a few new powers.
Spider-Girl was faced with other specters from her father's past, including the near-invincible Black Tarantula. The Tarantula arrived from South America to select May Parker as the perfect young woman to continue his bloodline. Creating "Team Spider" to supposedly assist May in her war on evil, he began a twisted mind-game to win May's heart, all the while seeking to strengthen his grip on New York's criminal infrastructure.
May has also fought versions of classic Spider-Man villains. She once fought the Savage Six, and has also fought Aftershock (Electro's daughter). She recently teamed up with Felicity Hardy, who has taken on the role of the Scarlet Spider. She also occasionally faces old villains from Spider-Man's past. She has faced Kaine, Venom, the Kingpin, the Hobgoblin, and Doctor Octopus, to name a few.
Recently, May experienced some of Kaine's power and they both saw a vision of her being stabbed to death in her red and blue costume. She started wearing her black costume to try to trick fate, but she was nevertheless stabbed by a Scrier in a battle. Near death, Normie gave her his symbiote (as a farewell gift, the symbiote healed Normie's scars and tattoos) and the symbiote healed May. In order to save May from the Hobgoblin, the symbiote (who turned out to be a she) drove the Hobgoblin away, but in the process was killed by his sonic emitter. Hobgoblin later escaped.
Whether facing old Spider-Man villains, newer versions of classic bad-guys, or completely new villains, Spider-Girl will always uphold her father's motto: With great power, there must always come great responsibility.