A new character, a tech - genius turned mad scientist. He has created a device that can control the minds of people through their cybernetic implants. He wants to use this power to rule Gotham and Nightwing and Batman Beyond must stop him. He could be an old acquaintance of Bruce Wayne who has a grudge against the Batman legacy.
The return of Slade Wilson (Deathstroke) could be a major plot point. He could have found a way to be revived in the 'Batman Beyond' time period. He's more dangerous than ever with new cybernetic enhancements and a vendetta against Nightwing and the new Batman. His military - like tactics and strategic mind would pose a huge challenge for the heroes.
Ink could be a great antagonist. He has the ability to manipulate his body into various weapons and forms. He could be seeking to take over Gotham's underworld in the 'Batman Beyond' era and sees Nightwing and Batman Beyond as threats to his plans.
Brother Eye could be a possible main antagonist. If it were to gain the ability to time - travel, it could try to rewrite history to create a world where it has complete control. It could manipulate events in different eras to eliminate any threats to its dominance, and Batman Beyond would have to stop it from achieving its goal.
Ink could be a great main antagonist. He has the power to manipulate shadows and could use this ability to create chaos in Gotham and beyond. He might target the Justice League and Batman Beyond because they represent order and he wants to spread his own brand of darkness.
The Batman Who Laughs could also serve as the main antagonist. He represents a twisted version of Batman, and his goal could be to infect all the Batverses with his madness. His knowledge of Batman's tactics and his own insanity would pose a huge challenge for the normal Batman as he tries to stop him from spreading chaos.
The Joker could be a likely main antagonist. He might be the one who manipulates the situation to get Batman arrested, perhaps by framing him for one of his own heinous crimes. The Joker loves to play mind games, and getting Batman locked up would be a huge part of that.
The Joker is always a great choice. He could come up with a particularly cruel and elaborate plan to put Batman in peril, like kidnapping all of Batman's allies and forcing him to choose which ones to save.
Perhaps an old enemy of Batman who has made a deal with Cadmus. They combine their knowledge and resources. This could be someone like Mr. Freeze, who has found a way to use Cadmus' genetic engineering to make himself even more powerful. His new form and abilities would pose a great challenge for Batman Beyond.
Another character could be Terry's love interest. She could play a role in the twins' story, perhaps she has a connection to their past or she gets caught in the middle of their conflict with Batman Beyond, making the story more complex and engaging.
It could be an evil ninja from Naruto's world who has somehow also gained access to the powers of the Beyond Two Souls world. This character could use these new powers to try and take over both worlds.
The Joker could be the main antagonist. Even though Batman is in jail, the Joker could find a way to continue his chaos - making. He might try to get into the prison to torment Batman or use the situation to his advantage by causing mayhem in Gotham City without Batman there to stop him.
Darkseid could be a potential main antagonist. He might view Superboy as a weapon that he wants to control. If he realizes that Batman is trying to shape Superboy into a hero of Earth, he would surely try to stop it. He could send his minions to attack Batman and Superboy or try to corrupt Superboy's mind from afar with his Omega Beams.