Madara Uchiha could be the main antagonist. Imagine if Madara somehow got a hold of some Kryptonite - like substance and used it against Naruto. He would see Naruto's Godlike powers as a threat to his plans of creating a new world order. Madara's Sharingan abilities combined with his knowledge of jutsu and his newfound way to counter Naruto's super strength and other powers would make him a terrifying and complex antagonist for Naruto to face.
It could be a combination of Orochimaru and Lex Luthor. Orochimaru from the Naruto universe is always seeking power and Lex Luthor from the DC universe is a brilliant but evil mastermind. They could team up, with Orochimaru being interested in Superman - like Naruto's unique physiology and Lex Luthor wanting to use Naruto's power to take over both the Naruto world and the DC world. They would be a formidable duo, constantly devising plans to undermine Naruto and his friends.
Darkseid could be the main villain. If Darkseid discovers the existence of Naruto in the DC - Naruto crossover fanfiction, he would see Naruto as a potential threat to his rule. Darkseid's Omega Beams could be a challenge for Naruto to avoid, and Naruto's ninja skills and super powers would be put to the test as he tries to protect both the DC and Naruto universes from Darkseid's tyranny.