The Kingpin could be a great antagonist. He could be trying to take over more of the city and sees Spiderman and Tigra as threats to his plans. He uses his criminal network and his physical strength to try and stop them.
It could be Doctor Octopus. He might have some new, more dangerous tentacle - like devices. He decides to target both Spiderman and female Spiderman because he views them as obstacles to his scientific experiments and his desire for power. He kidnaps some innocent people to lure them into his traps and tries to defeat them in a fight.
One idea could be that Spiderman and Tigra team up to stop a new super - villain in the city who has the ability to control animals. They combine their skills, with Spiderman's web - slinging and agility and Tigra's feline strength and senses.
The Green Goblin could be a great main antagonist in a dark fanfiction. He could be even more deranged and have a more elaborate plan to destroy Spider - Man, not just physically but also mentally by targeting his relationships.
The Joker could be a great main antagonist. Imagine he teams up with some of Spider - Man's foes like the Green Goblin. They could create a chaotic plan to take over both Gotham and New York. Their combined madness would be a huge threat to both Batman and Spider - Man.
It could be someone like Doctor Octopus who gets his hands on some ninja technology. He could use it to enhance his mechanical arms and also start stealing chakra from people to power his new devices. His scientific mind combined with the newfound ninja powers would make him a formidable foe for Naruto and Spiderman.
Venom could be a main antagonist in this crossover. If Venom were to find his way to Gotham, he would be a formidable foe. His strength and aggression combined with his alien symbiote abilities would make him a tough opponent. Batman would have to rely on his gadgets and strategic thinking, while Spiderman, having prior experience with Venom, would have to use his knowledge of the symbiote to try and stop it. And Venom's desire to spread chaos and destruction would put both heroes in a difficult situation.
Venom could also be a main antagonist. Imagine if he somehow got enhanced and became even more powerful. He could be causing chaos in the city, and both Spiderman and Deadpool would have to figure out a way to defeat him. Deadpool's lack of fear and Spiderman's knowledge of Venom could be key factors in their fight.
The Green Goblin could be a great antagonist. He might see the two spiders as a threat to his plans of taking over the city and decides to target them both. His maniacal nature and his array of dangerous gadgets would pose a serious challenge to Spiderman and Spider Girl.
The Green Goblin could also fit well. He could form an alliance with some of Wonder Woman's foes. His chaotic nature and love for destruction would contrast with the heroes' quest for peace. He could target both of them, trying to break their partnership and cause mayhem in the city.
It could be Doctor Octopus. Imagine he somehow gets his hands on some Sky High technology that enhances his mechanical arms and gives him new powers. He then decides to take on both Spider - Man and the Sky High students because he sees them as threats to his new - found power and his plans for world domination.