The Kingpin could be a great main villain. He could see the Civil War as an opportunity to expand his criminal empire. He could be secretly funding both sides in a way that makes the conflict worse, all while Spider - Man is trying to figure out his role in the war.
Mysterio could be another option. He could create illusions that make the situation between Captain America and Iron Man's sides seem even more dire. He could also target Spider - Man specifically, making it look like he's the one causing the most problems during the Civil War, when in reality it's all Mysterio's illusions.
It could be Mysterio. He's known for his illusions and deception. In the context of a civil war, he could use his powers to create false scenarios that make the heroes fight each other even more. He might pretend to be a hero on one side, but secretly be working to make the conflict worse for his own gain.
There's also a possibility that a new, original villain could be introduced. For example, a scientist who was wronged by the superhero community in the past and now wants revenge. He could create powerful weapons and technology that can counter the superheroes' powers, and he uses the divide in the Civil War to pick them off one by one.
Loki could be a great main villain. He could be secretly fueling the Civil War for his own gain, like trying to take over Asgard while everyone is distracted. He has the cunning and the motivation to do so.
A new supervillain could emerge. Maybe a scientist who got access to some of the leftover technology from the Civil War battles and uses it to create a powerful weapon. He then targets Spiderman because he represents the superhero community.
Well, one way could be that in the chaos of the Civil War, Spiderman might be caught in the crossfire between the two sides. Maybe he tries to stop a particularly violent clash and gets overpowered by the combined forces accidentally. Another possibility is that he's betrayed by someone he trusts on one of the sides, leading to his demise.
The Green Goblin could still be the main villain. He might see the transformed Spiderman as an easier target now that she's a girl, or he could be even more enraged by the change and be more determined to defeat her.
The Green Goblin could be a great main villain. He has a long - standing feud with Spiderman, and when the Avengers get involved, it could make the situation even more complex. His flying glider and pumpkin bombs would pose a serious threat to both Spiderman and the Avengers.
Maybe a biologist gone bad. He has been studying the worm and discovers that its cells can be used to create a powerful mutagen that can turn ordinary people into super - strong minions. He plans to create an army and take over the city. Spiderman has to stop him from using the worm in this way. And the worm, being an innocent creature, becomes a key piece in this battle between good and evil.
It could be Mysterio. He's a master of illusions. He might trick the Avengers into believing that Spiderman is a danger, using his illusions to make it seem like Spiderman is doing bad things. So the Avengers, thinking they're doing the right thing, kidnap Spiderman.
In the fanfic world, the public's reaction would be huge. Spiderman was a beloved hero. There could be mass protests against the superheroes and the Civil War in general. The remaining superheroes would have to deal with this public outcry while also mourning the loss of Spiderman. They might also start to question their own actions and the future of superhero - ing without him.