It could be a combined villain. For example, Orochimaru from the Naruto universe teams up with a powerful magic - user from Wanda's world who is jealous of Wanda's powers. This villain duo could be really menacing as they combine Orochimaru's dark jutsu and the magic - user's powerful spells.
Perhaps an ancient being that has the ability to manipulate both chakra and magic. This being was sealed away long ago in both the Naruto and Wanda's dimensions. But due to some events, it starts to break free. It sees Naruto and Wanda's combined powers as a threat and decides to target them first. It has the power to create illusions using both chakra - based and magic - based techniques.
It could be Orochimaru from Naruto teaming up with Dr. Eggman. Orochimaru is always seeking power and new forms, and Dr. Eggman wants to take over the world. Together, they could create some really dangerous machines and jutsu combinations to try and achieve their goals.
It could be Orochimaru from Naruto who somehow finds his way into the Lion King world. He would be interested in the unique magic and power of the Pridelands. He could try to control the lions or use them for his evil experiments, like he did with his human subjects in Naruto.
Perhaps a corrupted version of one of Naruto's comrades who has been influenced by the dark powers of Lucifer's world. This character would know all of Naruto's weaknesses and use them against him. At the same time, they would also have new demonic abilities, making them a formidable foe for both Naruto and Lucifer.
The main villain could be a rogue ninja who has somehow accessed the power of the Darksiders world. He has turned evil and wants to reshape both worlds according to his own twisted vision. He uses his ninja skills combined with the dark powers he has acquired to create an army of minions from both universes. Naruto and Fury must put aside their differences and use their combined skills to take on this powerful and unpredictable foe.
In this crossover, the main villain might be a combined form of Orochimaru from Naruto's world and Ares from God of War. Orochimaru's thirst for power and Ares' love for war could create a really evil and power - hungry entity. This villain could be trying to take over both the ninja world and the God of War realm. He would use his knowledge of ninjutsu and godly powers to cause chaos. Naruto and Kratos would have to put aside their differences and fight this powerful foe together. Kratos' brute strength and Naruto's strategic thinking would be essential in taking on this complex villain.
A new villain could be created specifically for this fanfiction. This villain could be a being that feeds on the chaos between the two different universes. It has the ability to disrupt chakra flow in Naruto's world and nullify magic in Lulu's world. Naruto and Lulu would have to figure out how to work together to stop this entity before it destroys both of their homes.
It could be a rogue shinobi who has found a way to enter the Matrix world and wants to take over both the real world and the Matrix. He uses his ninja techniques combined with the power of the Machines to create havoc.
Kabuto could also be a main villain in this context. He might see the potential in the gloves to further his own power - hungry goals. He could try to manipulate Naruto into using the gloves in a way that benefits him, or he could simply try to steal the gloves when Naruto is at his weakest.
It could be an evil Sith Lord who discovers the existence of the Naruto universe and wants to conquer it. He sees Naruto and Ahsoka's alliance as a threat and tries to stop them. This Sith Lord might use his dark side powers to corrupt some of the characters from the Naruto universe and turn them against Naruto and Ahsoka.
It could be Orochimaru. His thirst for power and his willingness to experiment on others would put him at odds with both Naruto and Deadpool. Orochimaru might see Deadpool's regenerative abilities as something to study and Naruto as a threat to his plans. He could try to capture them and use their powers for his own dark purposes.