The main villain could be Darkseid. Imagine if he somehow finds a way to enter the Naruto universe. He would be a formidable foe for both Naruto and Supergirl. His omega beams and immense strength would be a huge challenge for them to overcome.
A great choice for the main villain could be Brainiac. If he were to invade the Naruto universe, he'd start collecting all the knowledge and unique abilities there, including chakra. He'd see Naruto and Supergirl as threats to his plans. His vast intellect and robotic minions would make for an epic battle against the combined might of Naruto and Supergirl.
Lex Luthor would be a great choice. He could be plotting against both Batman and Supergirl. He might try to use his intellect to create a weapon that can nullify Supergirl's powers and outwit Batman's strategies at the same time.
Maybe an ancient evil spirit that has been awakened due to some mistake. It targets Ageha because she has a pure and powerful chakra. Naruto, being the hero he is, tries to fight the spirit, but he quickly realizes that he needs Ageha's help as well as the help of all his friends to defeat this powerful foe.
It could be a rogue ninja from the village with the Tenshikage. Maybe he's jealous of the Tenshikage's power and wants to take it for himself. He could be causing chaos in the village, stealing important ninja scrolls and attacking innocent villagers.
A new character could be introduced as the main villain. This character could be someone from an ancient clan that was once in control of the 10 - tailed beast but lost it. Now, seeing Naruto with that power, they want it back and will stop at nothing to get it. They could have unique powers and abilities that make them a formidable foe for Naruto and his friends.
It could be a new character, a powerful dark wizard who wants to use the combined power of Naruto's chakra and Pikachu's electricity for his own evil purposes. He creates all sorts of dark creatures and sends them after Naruto and Pikachu to try and capture them. He's very cunning and has a lot of minions to do his bidding.
Darth Vader could be a great main villain. His dark power and iconic status in Star Wars would make him a formidable foe for Supergirl. He could see her as a threat to the Empire's rule and try to eliminate her. His mastery of the Force and lightsaber skills would put Supergirl in a tough fight, especially if she's not familiar with the ways of the Force at first.
It could be a new character created specifically for this fanfic. Maybe someone who wants to steal Naruto's six - tailed power for themselves.
Another option could be a powerful shinobi from a forgotten clan that was once known for its wind - based abilities. This shinobi wants to revive his clan's former glory by any means necessary, even if it means going against Naruto and his friends. He could be using ancient wind - based techniques that no one has seen before, making him a formidable foe.
A powerful and mysterious organization could be the main villain. They have been secretly manipulating events in the ninja world for years, and now they plan to use a powerful weapon to destroy all the hidden villages and take over the world. Naruto has to expose and stop them.
A great option could be Orochimaru fused with Hades. Orochimaru's thirst for power and immortality combined with Hades' control over the Underworld would make a terrifying villain. He could be plotting to take over both the ninja world and the realm of Greek gods. He might use his dark jutsu and Hades' power over death to create an army of undead ninjas and mythological creatures.