A new and powerful Titan could be the antagonist. One that has been hiding in the shadows and now sees Percy alone as an easy target. Maybe this Titan has a special grudge against Percy and wants to take him down while he's vulnerable.
Perhaps an ancient and forgotten monster that has been awakened. It has no loyalty to any of the gods or other factions. All it wants is to destroy anything in its path, and Percy, fighting alone, is right in its way. This monster could have some strange and terrifying abilities that Percy has never faced before.
Well, in such a fanfic, Percy would probably have to dig deep into his own skills and experiences. Since he's alone, he can't count on Annabeth's strategic thinking or Grover's sensing abilities. He might have to face a god who's out to get him. He'd be forced to use his powers in creative ways, like using his water - control to escape from a labyrinth - like trap instead of having someone else to help him find an exit.
Maybe an ancient evil ninja who was sealed away long ago but has now been released. This antagonist could have powers that nullify any communication or summoning jutsu, forcing Naruto to fight alone. He would be extremely powerful and know many forgotten and deadly jutsu.
The main antagonist could be a powerful sorcerer who has found a way to enter the Percy Jackson game world. He has his own motives, perhaps he wants to steal the powers of the demigods for himself. He's able to manipulate the game's code to his advantage, creating illusions and false paths for Percy and his friends to follow. Or it could be an ancient spirit that was sealed away in the game but has been released. This spirit is angry at the gods and demigods and wants to destroy everything they hold dear. Also, a group of bandit demigods could be the main antagonists. They don't follow the rules of the game or the real - world demigod society and are causing chaos everywhere they go, trying to steal valuable items from both the game world and the real - world locations.
Nyx could be a great main antagonist. She's a primordial goddess of the night and Tartarus is her domain in a way. She might see Percy and his friends as intruders and try to stop them from leaving or achieving their goals. She could use her power over darkness and the unknown to create all sorts of obstacles for them.
It could be a new, powerful Titan that has emerged from the depths of Tartarus. This Titan might be seeking revenge on the demigods for imprisoning the other Titans and sees Hylla and Percy as the biggest threats.
A powerful sorcerer from another realm who uses assassins as tools. This sorcerer could see Percy as a threat to their plans of taking over the demigod world. They send their best assassins after Percy and also try to manipulate other demigods against him. They are extremely cunning and have a vast array of dark magic at their disposal.
The main antagonist could be a powerful Titan who wants to use Percy as a weapon to overthrow the Olympian gods. The Titan might see Percy's unique powers as a weapon as the perfect tool to gain ultimate power and reshape the world according to his own desires.
It could be Nyx. She is a very powerful primordial goddess in Tartarus. Since Percy is alone, she might see him as an easy target or a threat to her domain. Nyx could send all sorts of dark creatures and illusions to stop Percy from achieving whatever goal he has in Tartarus.
It could be a new dark wizard who is more powerful and cunning than Voldemort. This wizard might have been in hiding all this time, biding his time to take over the wizarding world. With Harry being alone, he would pose a great threat as Harry doesn't have his friends to support him in this fight.
Even some of the ancient demigods who turned bad could be antagonists. They might see Percy as a threat to their power or plans in the past. They could have different values and goals compared to Percy, leading to conflicts. For example, a demigod who was power - hungry and wanted to use time - travel to change things for his own gain, and Percy would have to stop him.