A powerful alien being with a hunger for anything that moves could be the antagonist. It sees Spider - Man as just another morsel to devour. It has the ability to create portals to swallow its prey whole, and Spider - Man has to figure out how to close these portals and defeat the alien before he becomes a permanent part of its diet.
Maybe a deranged genetic experiment gone wrong. This creature was designed to be a super - predator, and it has a natural instinct to 'vore' its prey. It targets Spider - Man because he's a threat to its hunting grounds. Spider - Man has to use his knowledge of science (maybe something he learned from Stark) to find a weakness in this genetic monstrosity and stop it from eating him and others.
Well, perhaps in a Spider - Man vore story, Spider - Man is exploring an alternate dimension where there are giant, voracious beasts. One of these beasts swallows Spider - Man whole while he's trying to save some innocent people. Inside the beast, he discovers a strange energy source that he can use to his advantage. He uses his strength to fight his way through the beast's insides, causing it to spit him out. Then he uses the knowledge of this new energy to enhance his suit and fight off any more threats in that dimension.
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.
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.
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.
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.
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.