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.
A symbiote - infected character could be the main antagonist. For example, if Harry Osborn gets infected by a symbiote. The symbiote enhances his already existing issues and makes him extremely aggressive. He becomes a powerful foe for Spider - Man, as the symbiote gives him enhanced strength, speed, and the ability to create weapons out of its black goo - like substance.
One possibility could be that a new villain emerges from the ashes of the previous game's events. Maybe a former Oscorp scientist who was inspired by the chaos and decides to create his own army of super - powered minions. Spider - Man would then have to not only face this new threat but also deal with the consequences of his actions in the first game on his personal life, like his relationships with MJ and Ned.
The Green Goblin could be a great main antagonist. He has a long - standing feud with Spider - Man. Maybe in this fanfiction, he could be out for a more brutal revenge after a particularly humiliating defeat. He could target Spider - Man's loved ones or try to completely destroy his reputation in the city.
The Green Goblin could be a great main antagonist even in a Spider Man reborn story. Maybe in this version, he has developed a new form of insanity - inducing gas that affects Spider Man's new powers. Another possibility is Doctor Octopus. He could have found a way to merge his mechanical arms with some sort of alien technology, making him far more powerful and a real threat to Spider Man reborn.
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.
Another option for the main antagonist in the fanfiction could be a jealous classmate. This classmate might be envious of Spider Man's popularity and powers. He or she could try to sabotage Spider Man at school, like spreading rumors about him or trying to get him in trouble with the principal. This would make Spider Man's school life even more difficult as he has to deal with both this classmate and any real threats to the city.
The Green Goblin would be a great main antagonist. His chaotic and unpredictable nature could pose a real threat to Spider - Man. He could have a new and improved glider and pumpkin bombs, and his goal could be to take over the city by causing mayhem and destruction.
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.