Personally feel more creators should realize how important their protagonist is. Especially for a multi-game series. But I'm just not a fan of changing protagonists for stories like this and see no reason to.
I suppose they got themselves into this bind when they made the series into a love story between Nate and Elena. It's a double edged sword because you increase engagement with the characters but also kind of build in their obsolescence.
So they kind of need another character to take over, and this time be careful not to fuck it up. If it were up to me I'd have one more game starring Nate, set relatively soon after the 4th game. Maybe Elena is in peril or something, or their young daughter (yeah, original I know). And I'd introduce some new character as the eventual replacement for Nathan, who could also eventually team up with Cassie. Because I don't think Chloe is going to cut it, and Sam is a bit of a clown.