I would like to see writers giving try to quartet once more,.
Four cast group is unexplored territory and its unknown if it could work out with more active character than Max was. And even though with three cast group writers showed how they are capable of keeping everyone active so that their presence could be felt, with four characters you set basis for wider type of interactions being present in main cast allowing that dynamic between characters flow in two different directions.
In Digimon its common practice to have 5 , often even more characters in one cast and no one is left out. One Piece exceeds that number to 10(and still counting), so im sure at least four cast group wouldn't be too problematic to handle if they decided to try.
However if they decide to do four characters group i feel that adding three new characters at once would be too much not leaving enough space and time to explore all of them individually. That's why in my opinion good idea would be mix of old and new, introducing one new girl and bringing one of older girl companions which are more mature and experienced to balance things out since with previously established companion you already have established groundwork and plots on which writers could just pick up doing continuation of his, her story.
That said i would like for 6th generation cast to be composed of Ash, two new characters and one of older ones being reused like Misty.
Her quirky tomboyish persona could mix well into such cast imo and it would be intriguing to see already somewhat experienced character growing forward providing certain spice into group chemistry with her spunky and outgoing attitude nowadays if hosos were something to go by.
We could also see her establish older sister relationship with new girls helping them in their growth since she is more confident and mature at this point. Going on journey at some point to advance goal of becoming water master learning new things, entering tournaments etc like Wallace trying to reach E4 position would seem like logical step forward and way to reintroduce her back.
Not to mention having two girls in same cast would be something unique to see allowing writers to explore on completely new concept and different interaction between characters.
Mix of old and new approach is often use in other anime like Bakugan to extent or Inazuma Eleven anime where older characters which are replaced come back to cast again at some point helping to push story of new characters forward through mentor role, while advancing their careers themselves.
So imo it could be worth a try, even though i know how this will likely stay just on wishful thinking.