A powerful monster from the demigod world that has a vendetta against Percy and Nico could be the main antagonist. It disguises itself as a teacher or a student and slowly starts to manipulate things in the school. It tries to isolate Percy and Nico from their friends and then attack them when they are at their weakest.
Well, one possible plot could be Percy and Nico having to deal with typical high school problems like bullies. Percy might use his water powers in a discreet way to stop them. Nico could be the mysterious loner at first but then make some real friends as he shows his cool powers. And they might also have to hide their demigod identities from the normal students.
In a fanfiction where they go to high school, Percy would likely be popular for his heroic deeds and good looks. He might join the swim team and break all the records. Thalia could be the cool girl who rides a motorcycle to school and gets into trouble for parking it in the wrong place. Nico would be the mysterious new kid. There could be a plot where they have to team up to stop a monster that is lurking in the school basement.
Perhaps an old enemy from Greek mythology who has found a way to infiltrate the school in a modern form. This could be a minor god or a powerful monster. They want to get revenge on Percy and Nico for past defeats. They might be using the school's resources, like the science labs or the library, to create chaos or find a way to regain their full power.
There's a chance that it's a new entity created by the imbalance between order and chaos. This entity is a force of pure destruction and wants to tip the scales completely in favor of chaos. Percy, Nico and Jason, with the help of Chaos, have to stop this entity from achieving its goal.
They would surely meet Harry Potter. Harry could be curious about their different magical abilities and background. Hermione would also be there, probably peppering them with questions about their own world's magic. Ron might be a bit skeptical at first but warm up to them eventually.
The camp leaders might betray them. If there is a power struggle within the camp, and Percy and Nico are seen as threats to the current leadership's power, the leaders could set them up. They could make it look like Percy and Nico are breaking camp rules or endangering the other campers, which would lead to the rest of the camp turning against them.
Well, perhaps Percy and Nico could be transferred to Hogwarts through some sort of magical accident. Maybe they'd have to deal with the different magical system there compared to their own world. They could make new friends among the Hogwarts students and get involved in the typical Hogwarts adventures like the Triwizard Tournament or dealing with a new dark threat.
Maybe a rogue ninja from Gaara's world who somehow follows him into the DxD highschool. This ninja could have a vendetta against Gaara and use the chaos of the DxD world to try and take him down. They could also team up with some of the devils who dislike Gaara's presence to create more trouble for him.
It could be a corrupted member of the mafia who has made a deal with a rogue group of fallen angels. This person betrays his own mafia family and works with the fallen angels to create chaos in the Highschool DxD universe. He is very sly and manipulative, always staying one step ahead of the heroes. For instance, he uses his knowledge of the mafia's operations and the power of the fallen angels to set traps for the protagonists.
Sasuke could be the main antagonist. In high school, he might be jealous of Naruto's popularity or newfound skills. He could try to undermine Naruto at every turn, just like their complex relationship in the original Naruto series.