There could be a new type of deity or demi - deity who has a vendetta against Percy specifically. They believe that demigods should be locked away in mental hospitals to keep them from causing chaos in the mortal and divine worlds. So they set up this hospital as a prison for Percy and any other demigods that cross their path, and Percy has to fight against their ideology and power to break free.
Perhaps a powerful monster in disguise as a doctor or staff member. They could be using the hospital's resources to create a portal to the underworld or something equally dangerous, and Percy has to stop them. They would be constantly trying to drive Percy crazy or keep him from interfering with their plans.
It's possible that the main antagonist is a new mythological creature that has the ability to manipulate minds. It has lured Percy and other demigods to the mental hospital and is slowly driving them insane in order to feed off their fear and chaos energy.
Well, he might meet other characters who also claim to have had strange experiences. They could form a sort of alliance, thinking they are all in the same boat, not realizing Percy's experiences are real in the context of the Percy Jackson universe. They could plan an escape together, believing they are being wrongly held.
Another possibility is that Percy has suffered some sort of mental trauma from his battles. He's having nightmares and flashbacks, and his friends think the mental hospital can help him. But once inside, he realizes that there are dark forces at work in the hospital. He has to use his demigod powers subtly to protect himself and the other patients from these unseen threats.
It could be a power - hungry Atlantean noble who wants to rule not just Atlantis but also the surface world. He sees Percy as a threat to his plans and tries to stop him at every turn.
A new and powerful demon that has emerged from the darkest corners of the underworld. This demon is bent on using Percy's connection to the overworld to break through the barriers between the two worlds and unleash chaos. It has powers that are different from what Percy has faced before, like the ability to manipulate the very essence of the underworld's environment.
A powerful Amazonian sorceress who has turned against her own kind and is now trying to use dark magic to take over the world. She could see Percy as an obstacle in her path and constantly try to defeat him.
Maybe it could be a demigod who has become obsessed with power through gaming. This demigod, let's say a child of Hades, discovers a way to use dark magic and combine it with gaming technology to try and rule over all the other demigods. He sees Percy as a major threat to his plans because Percy is so popular and has strong powers, so he constantly tries to undermine Percy at every turn.
The goddess Hera might also be a great antagonist. Since she has a history of interfering in the lives of demigods, she could be jealous or threatened by Percy's rebirth. She might try to stop him from reaching his full potential in his new life or cause trouble between him and his new allies.
A powerful demigod who has been corrupted by the idea of primordial power could be the main antagonist. They might believe that by allying with a primordial or obtaining their power, they can become greater than the gods. This demigod would then oppose Percy, who stands for the protection of the current order.
An ancient and forgotten god who has been awakened. This god could be angry at the modern demigods for ignoring the old ways and decides to send assassins after Percy as a warning to the rest. They might want to bring back the old order where gods were feared and worshiped more and see Percy as a symbol of the new, more independent demigods.