Right now, I can only see Kyrie as a supportive character. She has no power, and her personnality is set to your average ultra kind girl in DMC 4 (and she almost doesn't exist in DMC 5). Just flipping her into a villain won't do, and having her kidnapped as the main event for Nero to go and save her would be DMC 4 all over again.
She need to go outside and be confronted to hard choices while not having the game being all over her. Like having her adopted kids being lost during an demon invasion, and Nero busy trying to stop the invasion so she can't just call him to do things for her. She then would go alone to try to take back the kids.
Maybe having Vergil return in the human world and being in Fortuna, and choosing to help her as he try to change his attitude. At this point, neither Vergil or Kyrie would know each others, so Kyrie would be afraid of Vergil ruthless actions and lack of emotion. But she would guide him through the city and try to stop him when he's being ruthless. At the end, Kyrie would have to make an hard choice, like either saving the 3 kids or saving a bunch of Fortuna's people (like 10 of them, adult and kids). And no time to think since Vergil would choose the lesser evil and save the maximum amount of people and already being on his way to save the biggest group. So she would stop him and ask him to go for her kids instead, which Vergil would do, and condamn the other group.
That's somewhat of a generic hard decision, but Kyrie is such a blank character that I can't think of anything else for her.