I think Orochimaru would also be a strong candidate for the villain. He has always been interested in unique powers. When he sees The Flash's speed and the different nature of the speed force, he would be very tempted. He could try to experiment on The Flash or use his own jutsu to trap him. And of course, he would see Naruto as an obstacle in his way of obtaining this new power source.
Kabuto could be a likely villain. He's very intelligent and has a thirst for power. He could use his knowledge of jutsu and his ability to manipulate others to try and steal The Flash's speed force. He might think that by combining it with his own powers and ninja techniques, he could become invincible.
In this kind of crossover, Reverse - Flash would be a great villain. He could see Naruto's powers as something to be conquered. He might try to use his speed to outmaneuver Naruto and steal his chakra. Also, he could create chaos in both Naruto's world and The Flash's world by changing timelines and causing rifts between the two universes.
Lex Luthor could be a great villain. He might be jealous of Supergirl's powers and see Flash as an obstacle in his plan to defeat her. He could use his scientific knowledge to create some sort of weapon that targets both speedsters and Kryptonians.
The Reverse - Flash would be really interesting. He could target both Batman and the Flash. For the Flash, he's a long - time nemesis, but for Batman, he'd be a new and extremely dangerous threat. His ability to manipulate the speed force and time could put Gotham in chaos in ways Batman has never seen before. And he could use his knowledge of the Flash to try and set traps for both heroes.
Reverse - Flash could be really interesting. He could manipulate time in ways that not only affect Flash but also Supergirl. For example, he could go back in time and prevent Supergirl from arriving on Earth, which would change the whole timeline. Flash would then have to convince her to come to Earth again while also dealing with Reverse - Flash.
Darkseid is another option. His power and his desire to conquer Earth could bring Batman and Superman together. He could target both Metropolis and Gotham, and his presence would require the two heroes to combine their skills. Batman's strategic mind and Superman's brute strength would be needed to face this powerful foe.
I think Eobard Thawne, the Reverse - Flash, could be really interesting. He could use his speed to try and steal Danny's ghost powers. His devious nature and time - traveling abilities would make him a formidable foe. He might see Danny's powers as a way to enhance his own and become even more powerful. And Danny would have to use his unique ghostly skills, like his ability to phase through objects and fly, to outwit the Reverse - Flash.
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.
Ra's al Ghul could be a great villain. He is always seeking power and immortality. In a crossover, he might see the potential in mutant genes to achieve his goals. His vast resources and knowledge would make him a formidable foe for both Wolverine and Batman. He could be plotting to use mutants in some grand scheme that would also impact Gotham, which would draw the attention of both heroes.
A powerful ancient demon that has been sealed away for centuries could be a great villain. This demon could have the power to manipulate time and space, which would make it a formidable foe for both Dante and Bayonetta. It could be awakened by some dark magic ritual gone wrong in both of their worlds, and its goal could be to merge the two worlds into a chaotic realm of darkness where it can reign supreme.
It could be someone like Frieza. Frieza is extremely powerful and evil in the Dragon Ball universe. If he somehow found his way into the Naruto universe or if the fusion character was in the Dragon Ball universe, he would be a great threat. His ability to transform and his cold - blooded nature would make him a tough opponent for the fusion of Goku and Naruto.