In the extended secret ending, we learn that Kachi is actually Achi. The same Achi from the first game, who wanted to use Saki to help her destroy gods. Isa's continued protection of Kachi is probably going to result in him doing that very same thing, going up against the Creators. Now consider that maybe, just maybe, Achi/Kachi never actually lost her memory in the first place...
Which would mean that Kachi's personality was all an act, and she knew exactly how Isa would respond, thus making it a Batman Gambit of sorts.
Of course, the question still remains as to whether or not she should be viewed as evil for this deception. The Creators don't exactly seem like the greatest people ever, seeing as the Nebulox are pretty nasty. Achi's means in the first game, bringing about the apocalypse just to get her super-soldier Saki, are frightening and evil (it only seems as if she is doing it for her own good). Fighting alongside Isa to bring down potentially cruel masters... that might not be as bad.
Consider, though, that Isa may very well have been told by his mother, Airen, about Achi, and how his father became that way. He may side with Achi, simply because he has seen the evil of the "creators," but he might be a bit more wary of her. Can we get a sequel, please?
According to the European release website, his mother never mentioned Achi specifically, she simply told him not to get mixed up with "gods"(the creators) or "holy women"(the things from outer space). Of course, if he learns she specifically caused his problems and nearly murdered a planet...
(It could be interpreted that the Nebulox were trying to protect their homeland from an evil invader, Achi, who in the past had tried to kill billions of people, and a traitor, Isa, who had (unwittingly) joined her wicked scheme. So the whole time, Isa may have been fighting and killing the good guys...)
Of course, the Nebulox aren't exactly the nicest people themselves. They were perfectly willing to destroy the entire planet just to kill Isa and Kachi. Perhaps they believed that it was worth it to destroy Achi, as they thought her a threat to the universe, but that's still pretty damn extreme.
As far as the characters know, Achi died in the last game. She didn't. Isa has been fought outer space beings awhile before he met Kachi if the manual is to be believed but who's to say he, or any other soldier has actually killed one? While Achi does seemed to be worried about taking on a god/creator it doesn't change that she shrugged off an Earthshattering Kaboom. Kachi seems like she can be killed but that may be because of her memory loss, considering she's the same as Achi. Given this, humanity is only there to keep outer space monster attention long enough for the "gods" to catch them. This is why they always ended up making peace, because they realized they could not win but they were killed off anyway when the other things impossible for them to win against showed up.