It could be a corrupted version of an old ally. For example, a former S.H.I.E.L.D. agent who was exposed to some strange space radiation. This has turned him evil and he now wants to use his knowledge of Earth and his new - found space powers to create chaos. He blames Spider Man for not being able to save him from the radiation and is determined to make Spider Man pay, all while causing destruction across the galaxy.
Perhaps Doctor Octopus. But instead of just having mechanical arms, his mutation gives him the ability to control any metal object in the city. He wants to take over the city using his newfound powers and sees Spider - Man as the only obstacle.
It could be the Green Goblin. In the sequel, he could return more powerful and with a new plan. Maybe he has found a way to enhance his strength and insanity using some new Oscorp technology. He could target Spider - Man not only for revenge but also to prove his superiority over the web - slinger.
The Green Goblin could be a great main antagonist. Imagine in this other world, he has even more advanced gliders and pumpkin bombs. He could be ruling over a part of the city with his goblin minions, and Spider Man has to stop him from spreading his reign of terror further. His maniacal laugh and unpredictable nature would make him a formidable foe in this new world.
The Kingpin could be a likely antagonist. He has the resources and the motive to frame Spider Man and get him out of the way. He could use his criminal connections to plant false evidence and make sure Spider Man ends up in jail.
It could be the Green Goblin. He might manipulate Spider Man in some way, perhaps by tricking him into believing that the only way to protect the city is to rule it with an iron fist. This would slowly corrupt Spider Man's good intentions.
The Green Goblin would be a great choice. He's always been one of Spider - Man's most dangerous foes. With Spider - Man unmasked, the Green Goblin could use this to his advantage, attacking not just Spider - Man but also those close to him, knowing that Spider - Man will be more vulnerable because he has more to lose now.
Green Goblin is another option. He might take advantage of the divided superhero community. He could target Spider - Man specifically, knowing that with the other heroes at odds, there's less chance of them coming to his aid. He could also try to use the conflict to his advantage in his criminal activities, like stealing from places that are unguarded because the heroes are busy fighting each other.
It could be a character like the Hobgoblin. He's a classic Spider - Man villain and would bring a lot of chaos to the story.
Doctor Octopus could be a great main antagonist. He could upgrade his mechanical arms and team up with other villains. His intelligence and his ability to create complex machines could pose a serious threat to the Avengers and Spider - Man.
An anti - hero or a morally grey character might be the antagonist. This character could have a different view on relationships and superhero life. He convinces Spider Man that the harem is holding him back from achieving greater things. And Spider Man, being influenced, betrays the harem.