Perhaps a rogue demigod who has made a deal with a speed - based meta - human villain from the Flash's world. Together, they plan to take over both the magical realm and Central City. The demigod could use his powers in combination with the meta - human's technology to create some really tough challenges for Percy and the Flash.
It could be a god who is angry at the mixing of the two worlds. This god decides to use his powers to disrupt both the Flash's world and Percy's world of demigods. He might create natural disasters in Central City and summon mythical beasts in Percy's world, forcing Percy and the Flash to stop him.
The Riddler could be a great main antagonist. He could create puzzles and traps that are based on both the Flash's speed and Gotham's dark secrets. For example, he might set up a trap where the Flash has to run through a maze of moving walls in Gotham while also solving riddles that are related to Batman's past.
The Reverse - Flash would be a great antagonist. His time - traveling abilities and his vendetta against the Flash family could make for a really intense story, especially if he teams up with other villains from the Kid Flash's universe in a crossover.
Maybe the Reverse - Flash. He could somehow cross over into the Percy Jackson world. He'd be a difficult adversary for both Percy and Flash. He could use his negative speed force to slow down Percy's reflexes and disrupt Flash's connection to the speed force. Percy would have to rely on his wits and the power of the sea to fight back, while Flash would have to find a way to overcome the Reverse - Flash's power - draining abilities.
It could be a powerful mage who wants to use Percy's demigod powers for his own evil plans. This mage might be jealous of Percy's unique abilities and try to control him.
It could be a character who is jealous of the power that could come from combining the two worlds. Maybe a rogue demigod who wants to use Jessie's knowledge of her world's technology and the magic of the Percy Jackson world to rule over both. This character might start causing problems by stealing important artifacts from both worlds to try and build a device that would give them ultimate power.
Darth Vader could be a great main antagonist. His power in the Force and his imposing presence would be a huge threat to The Flash. He could try to capture The Flash to study his speed abilities for the Empire.
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.