One of the more intriguing possibilities is Adriana Soria, better known as the Queen. She's traditionally been a relatively minor villain, taking on Spider-Man and Captain America, but became a major player in Dan Slott's "Spider-Island" event.
Adriana Soria was part of the Women's Army Auxiliary Corps back during World War II, but was exposed to radiation at Bikini Atoll. This triggered a latent mutation, but also broke her mind. Decades later, she escaped - still young, as her aging had been slowed. Disturbingly, because Spider-Man possessed an arachnid genome he is subject to the Queen's mental control.
"Spider-Island" was the Queen's finest hour. She was the mastermind behind an infestation of spider-powers in Manhattan. Her insane plan was to mutate the entire population of New York into spiders, which she could control with her will. As more and more people fell thrall to the Queen's control, her powers began to increase exponentially. She was only defeated when Spider-Man released an antidote to the so-called "Spider-Flu," weakening the Queen to the point where she could be killed.
The Queen would be an appropriate villain for one simple reason; she could be used to grant new characters spider-powers. Homecoming already dropped references to Miles Morales, better known to comic book fans as the Ultimate Spider-Man. Gwen Stacy has recently been reinvented as Spider-Gwen, an alternate-universe version of the character fans know and love from the classic Spider-Man comics. Were Marvel to involve the Queen, they could easily create both Miles Morales's Spider-Man and Spider-Gwen.
To finish off, let's use an unusual example: the character known as Joystick. She was introduced as a supervillain participating in the so-called "Great Game." These villains were sponsored by wealthy corporate figures, and were paid to take on superheroes - or even one another. If they triumphed, they got paid; their corporate sponsors shared in their winnings. The majority of Joystick's enemies were related to Spider-Man, including his clones Kaine and the Scarlet Spider.
Joystick eventually became a member of the Thunderbolts, although she swiftly betrayed the super-team. In Thunderbolts #102, she demonstrated just how powerful she really was; Joystick proved easily able to evade attacks from a super-speedster. She used her own superhuman agility and reflexes to easily win the battle, ultimately breaking the speedster's legs. No doubt she would prove a terrifying threat for Spider-Man, while the Great Game might explain her being overseas.
Of these possibilities, Jessica Drew seems the most likely. At the same time though, the Queen would be a particularly powerful enemy; she could also play an important role in the MCU, setting up the next generation of Spider-powered heroes.
It's worth remembering, though, that Spider-Man: Homecoming was willing to dramatically reinvent some of Spider-Man's secondary characters. Zendaya played a version of Mary-Jane, for example, while Liz Allen was redesigned as the Vulture's daughter. Given that's the case, it's quite possible Marvel could deliberately reinvent another character as a "femme fatale" for the Homecoming sequel Ultimately, it's likely that fans will only get a solid answer when Marvel announce some casting decisions.
- Black Panther (2018) release date: Feb 16, 2018
- Avengers: Infinity War / The Avengers 3 (2018) release date: Apr 27, 2018
- Ant-Man & The Wasp (2018) release date: Jul 06, 2018
- Captain Marvel (2019) release date: Mar 08, 2019
- Spider-Man: Far From Home (2019) release date: Jul 02, 2019
- The Avengers 4 / Avengers: Endgame (2019) release date: Apr 26, 2019