Danzo might be the main villain. He's known for his underhanded tactics. He could have banished Naruto to create chaos and then sent his Root agents to destroy Konoga for some political or power - related reasons. He might see Konoga as a threat to his control over the village in some way.
A new, powerful and mysterious villain could be introduced. This villain has a vendetta against Konoha (where Naruto is from) and Konoga for some past event. He manages to get Naruto banished by manipulating the village elders and then destroys Konoga as part of his grand plan to weaken the region and gain power.
One possibility is that Naruto is banished because of a false accusation. Konoga is a place that has some important secrets or power sources. Villains target Konoga to gain that power. Since Naruto is banished, he's not there to protect it. The fanfic could detail how Naruto, once he finds out about Konoga's destruction, decides to return and face the villains, even if it means going against the village that banished him.
It could be Shao Kahn. Since Naruto is an outsider in the Mortal Kombat world, Shao Kahn might see him as a threat or just a toy to play with. He could be the one who wants to either kill Naruto or use his power for his own evil plans.
Another option for the main villain in a Naruto banished Mass Effect fanfiction could be a power - hungry Spectre. This character could be jealous of Naruto's abilities and popularity among the different species. He'd use his position and resources to frame Naruto and turn the various races against him, all while he secretly plots to gain more power and control in the galaxy.
It could be an original character created by the fanfic author. This character might be a skilled fighter, maybe with a unique weapon or fighting style, like using a special kind of kunai combined with lightning - based chakra attacks.
It could be an original character. For example, a ninja who was born into a minor clan but had great potential. However, due to political intrigue and jealousy from a major clan, he was framed and banished. He then became a mercenary to survive. Another option could be a character who was once a part of a secret ninja organization and was banished when he disagreed with their methods. Now, as a mercenary, he returns to the Naruto world with a vendetta against those who wronged him.
The main antagonist could be an old - school ninja who believes in the traditional and often harsh ways of the ANBU. They see Naruto's actions as weakening the village and set out to oppose him at every turn, trying to bring back the old ANBU regime.
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.
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.
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.