Lex Luthor would be a great antagonist. He could see Superboy as a threat to his plans in Metropolis and try to find ways to discredit him or even eliminate him. Since Lois is a journalist, she might start to investigate Lex's actions against Superboy, which would put her in danger as well.
Lex Luthor could be a great main antagonist. He could be jealous of their combined power and see them as a threat to his plans of world domination. He might create some high - tech weapons specifically designed to counter their abilities.
Madara Uchiha could be a great antagonist. His powerful Sharingan abilities and his grand plans for the Naruto world would put him at odds with Supergirl. He might see her as a threat to his control and try to manipulate or defeat her. Another option could be Kaguya Otsutsuki. Her god - like powers and desire to reshape the world would clash with Supergirl's values and her attempts to protect the people of the Naruto universe.
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.
It could be an evil ninja from Naruto's world who somehow gains Kryptonian - like powers. He becomes power - hungry and decides to take over both the Naruto world and Supergirl's world. His knowledge of ninja techniques combined with super strength and other abilities would make him a formidable foe.
Lex Luthor could be her main antagonist. He might see Dark Kara as a threat to his own plans of world domination. He could try to manipulate her into doing his bidding or, if that fails, find ways to destroy her. Another option is Brainiac. Brainiac might be interested in studying Dark Kara's new form and powers, and in the process, they could end up in a battle as Kara resists being his experiment.
One possible villain could be Bizarro. Bizarro is always causing chaos and with Superboy and Superman together, it would be an interesting fight. Bizarro's reversed logic and powers would make it a tough battle for them.
One idea could be that they team up to face a new and powerful villain from another dimension. This villain has the ability to nullify their powers temporarily, so they have to rely on their wits and non - superhuman skills. Another plot could be that they discover a long - lost Kryptonian artifact that holds the key to saving Earth from a natural disaster, but they have to solve a series of complex puzzles to unlock its power. Or perhaps they meet in a situation where they initially don't recognize each other as Superboy and Supergirl, and there's some humorous misunderstandings before they figure it out.
It could be a powerful alchemist who has gone rogue and wants to use Naruto's chakra for some dark alchemy purpose.
There could be an ancient force that is awakened by the meeting of Harry and Hela. This force wants to destroy both of them because their combined powers could potentially stop it from achieving its goal of spreading chaos and destruction throughout all the realms. It would use all kinds of devious means to try and separate them and defeat them one by one.