It could be a new powerful monster that was sent after Percy because his mom was no longer there to protect him. Maybe a monster that has a grudge against Percy's family.
It could be one of the camp leaders who turned against Percy. Maybe they are jealous of Percy's popularity among the other demigods or they believe he is a threat to their power within the camp. So, they manipulate the situation to make it seem like Percy has done something wrong and get him abandoned.
Well, in such a fanfic, perhaps Percy ends up in a new camp or place full of demigods he doesn't know. He has to prove himself without his mom's support. He could befriend some unlikely characters who help him understand more about his mother's disappearance. And in the end, he might find that his mom left to protect him from a greater threat that he now has to face on his own.
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 a vengeful god. Maybe a god who feels that the sister's existence is an insult to their power. So they set out to stop Percy from finding her. For example, Hades might be the antagonist if he believes that the sister's return could disrupt the order in the Underworld.
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.
It could be an old enemy who now sees Percy as an even greater threat. Maybe Kronos' remnants. Since Percy is now a god, they might fear that he'll be able to fully destroy them. So they try to stop him from getting used to his powers or try to steal his powers.
A powerful Titan who wants to use Percy's newfound power as the God of Pain for his own evil purposes could be the main antagonist. This Titan might see Percy as a tool to spread chaos and destruction, and he tries to manipulate Percy into using his pain - based powers to harm innocents. Percy would then have to resist this Titan's influence and fight against him.