Considering OS Ash's personality and the original nature of the anime, a girl like Akane (Ranma 1/2) would work better as the lead girl.
This is probably why the original series and DP series worked so well since Misty & Dawn's dynamic with Ash was somewhat similar to Ranma & Akane. JN series could have work well with a female OC that is prettier than May/Serena who is forced to be a research fellow with Ash as they fight like Ranma & Akane.