It could be a combined force of Orochimaru and some of the power - hungry nobles from Code Geass. Orochimaru is always after power and knowledge, and the nobles in Code Geass are often corrupt. Together, they could create a really formidable enemy for the heroes.
Madara Uchiha could be a great main villain in such a crossover. His already powerful ninja abilities combined with the potential of getting a Geass power would make him extremely dangerous. He could use Geass to control other ninjas and make them fight for his cause, like creating an army of mind - controlled shinobi to take over the world.
It could be a new character who is a mix of Naruto and Lelouch. He has Naruto's determination and Lelouch's intelligence. This character could be the center of the harem, with his unique personality attracting female characters from both universes.
Another possibility is that the main antagonist could be an organization within the Britannian Empire that is secretly pulling the strings. They might see Lelouch and Leila as a threat to their hidden agendas. This organization could be using underhanded tactics like assassination attempts, spreading false rumors, and creating internal conflicts within Lelouch and Leila's alliance to try and bring them down.
Lelouch would be really interesting. His complex personality and his ability to manipulate with Geass would make for some great interactions with Naruto. He could try to use Geass on Naruto, but Naruto's strong will might resist it, leading to a power struggle of sorts.
Perhaps an ancient evil that has been sealed away in the empire for centuries but is released due to the chaos of the crossover. This entity could be more powerful than any foe the Naruto characters have faced before, forcing them to find new ways to fight.
A group of rogue shinobi and some of Daria's school bullies could team up. The shinobi would give the bullies some ninja powers, and together they would cause trouble in both worlds. This group would be difficult to deal with as they combine the physical strength of the shinobi with the local knowledge of the bullies.
Another possibility is a corrupted dragon spirit that has been awakened due to the mixing of the two worlds. This spirit could be spreading chaos and trying to destroy both the ninja world and the dragon world. Naruto would have to figure out a way to stop it, as it has powers that are beyond what he has faced before.
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.
Madara Uchiha would also make a great antagonist. Imagine if he was resurrected and saw Naruto with Samehada as a threat to his plans of creating a new world order. He would use his Sharingan and Rinnegan powers to try and take Samehada from Naruto, believing that with it, he could easily defeat all who oppose him and reshape the ninja world according to his will.
Maybe another kitsune who has gone bad. In the fanfiction world, there could be a rogue kitsune who sees Naruto as a threat. This antagonist kitsune might be jealous of Naruto's power or his connection to the human world. They could try to undermine Naruto's attempts to protect the village or his friends.