A powerful wizard or sorcerer could be the main antagonist. They might have a grudge against the man for some past wrong, real or perceived, and used their magic to make him disappear. In the fanfiction, they would try to prevent anyone from finding him and might cast various spells and illusions to thwart the heroes.
An alien race could be the antagonist. If the story has a science - fiction element, the man could have been abducted by an alien race for experimentation or some other purpose. The aliens would then try to stop any attempts to rescue the man from their clutches, using their advanced technology against the humans in the story.
A powerful tech - genius who has a grudge against the man of iron could be a great antagonist. Maybe this person was once rejected by the same company that made the man of iron's suit and now wants to prove that he is better.
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.
Madara Uchiha could also be the main antagonist. Even if he was defeated before, in this fanfiction, he could come back with a new plan related to the Ten - Tails. He might want to use Naruto as a vessel to fully revive himself and then take over the Ten - Tails' power.
Dr. Wily would be a very likely main antagonist. He could be using time travel to his advantage, for example, going back in time to steal important technology before Dr. Light discovers it. This would give him an even greater edge in his evil plans in the present or future.
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.
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.