Perhaps an ancient evil spirit that has been sealed away for centuries and has a connection to the Uchiha's past. It targets the Uchiha clan because of their special abilities and Naruto because of his status as a Jinchuriki. It slowly corrupts some of the Uchiha members to do its bidding and starts a war in the ninja world.
It could be a rogue Uchiha who has turned against the clan's values. He might be jealous of Naruto's power and popularity, and decides to use his Uchiha abilities to create chaos in the ninja world. He could also be trying to revive an old and dangerous Uchiha - related technique that was sealed away long ago.
I think Naruto and Itachi could also be main characters in this fanfic. Naruto might look up to Itachi for his self - sacrifice and powerful abilities. Itachi could act as a mentor - like figure to Naruto in the context of the fanfic, guiding him in understanding the Uchiha clan better.
A new character could be created as the antagonist. For example, an Uchiha who has been corrupted by the power of the Sharingan and wants to use Naruto's special Uchiha - related abilities for his own evil purposes. This character could be jealous of Naruto's unique position within the Uchiha - related story and try to take it from him.
Sasuke Uchiha could be a great choice as the main character. He already has a complex backstory and a lot of room for character development. His journey from seeking revenge to finding his own path in the Naruto series can be further explored in a fanfic.
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.
Madara Uchiha could also be a main villain in this crossover. He could be interested in the power of the Triforce in the Zelda world. He might try to manipulate Link and Zelda to get to it. His Sharingan abilities would make him a formidable opponent in the world of Zelda, and his large - scale plans could involve taking over both the Naruto and Zelda universes.
A powerful demon named Malice could be the main villain. He has the ability to absorb both chakra and ki, making him a formidable foe for Naruto and Goku. He has a dark plan to destroy both the Naruto universe and the Dragonball Super universe and create his own realm of chaos.
It could be Orochimaru. He has always been interested in dark and forbidden jutsus. He might have found a way to create the 'mob of the dead' situation to test his new powers or to capture Naruto for his own purposes. He could use his snake - like minions along with the undead to create chaos.
Maybe a rogue ninja who has learned about modern technology and uses it to his advantage. He could be stealing valuable ninja artifacts and using modern gadgets to cover his tracks. He's smart like the villains in Case Closed, but also has the power of a ninja. He would be a difficult opponent for Naruto and Conan to face as he can blend the two different worlds' tactics.
A powerful dark wizard could be the main villain. He could be jealous of the clone's unique powers and want to steal them for himself. He might use dark magic to try and corrupt the clone or simply try to destroy it to prevent it from becoming too powerful.
Perhaps a powerful and unknown shinobi from a far - off land. This shinobi has heard of Team 7's reputation and sees them as a threat to his plans of world domination. He uses his unique and mysterious jutsu to challenge Team 7 at every turn, and they have to figure out his motives and weaknesses to stop him.