Joker could be a main villain in an interesting way. He could somehow get his hands on some speed - based technology or drug that gives him super - speed for a short time. He then uses this new - found ability to create chaos in both Gotham and Central City, taunting both Batman and the Flash. His unpredictable and insane nature would make it very difficult for the heroes to anticipate his next move.
Ra's al Ghul would also be a suitable main villain. He might be interested in the Flash's speed for some dark purpose, like using it to spread a deadly virus across the world quickly. He could set up a complex plan that involves both Gotham and Central City, forcing Batman and the Flash to team up. Ra's al Ghul's long - term goals and his vast resources would make him a formidable opponent for the two heroes.
The Reverse - Flash could be a great main villain. He could travel to Gotham to cause chaos and draw out the Flash. His time - manipulation abilities would pose a huge threat not only to the Flash but also to Batman's carefully planned strategies in Gotham. Batman would have to adapt to dealing with a villain who can move at super - speed and mess with time.
A new meta - human villain created specifically for the crossover could be interesting. This villain could have the power to control shadows and use them to move quickly, mimicking the Flash's speed in a way. In Gotham, he could use the city's many dark corners and alleys to his advantage. He could also be a master of disguise, fooling both the Flash and Batman. His motives could be to take over both Gotham and Central City and create a new world order where meta - humans rule over normal humans.
The Reverse - Flash would be really interesting. He could target both Batman and the Flash. For the Flash, he's a long - time nemesis, but for Batman, he'd be a new and extremely dangerous threat. His ability to manipulate the speed force and time could put Gotham in chaos in ways Batman has never seen before. And he could use his knowledge of the Flash to try and set traps for both heroes.
Kingpin would be a very suitable main villain. He has his criminal empire in Hell's Kitchen already, and if he decides to make a move on Gotham, it would bring him into conflict with Batman. His power, wealth, and ruthlessness would make him a formidable foe for the two heroes to face together.
A good main villain could be Brother Eye. It's a powerful and menacing artificial intelligence. In a crossover, it could have evolved in the future to be even more dangerous. It could pose a threat to both the future world of Batman Beyond and the past era of the Justice League, forcing them to team up to take it down.
The Reverse Flash could also be a main villain in this crossover. He travels to the Smallville universe to cause trouble. He might target Clark, thinking that by eliminating him early, he can change the future in his favor. This would force Barry and Clark to work together to stop the Reverse Flash's evil plans.
The Riddler could be a great main antagonist. He could use his intellect to create puzzles and traps that not only challenge Batman's detective skills but also the Flash's speed. For example, he could set up a series of time - locked puzzles where the Flash has to use his speed in a very specific way at specific times to unlock them, while Batman has to figure out the overall pattern of the puzzles.
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 speedster from another universe who has come to challenge Flash. This villain might have some unique powers related to speed that Flash has never encountered before, like the ability to steal speed from other objects or people.
The Joker could be a main villain. He might see Izuku as a new plaything and try to break his spirit during his training with Batman.
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.