@Chancey289 brought the idea of a new female protagonist in the "are you done hoping" thread and I wouldn't mind a new cast for a spinoff.
The one we have has started to wear out their welcome so some new blood could be worth it. Granted a DMC5 should focus and hopefully conclude Dante's story but a spinoff is fair game.
I think the key is creating someone who could stand apart from Dante as a foil and be unique as well in terms of motivation, powers etc.
Nero felt more of the same which is why people didn't take to him as easily.
EDIT- there are things that make him different but they weren't really highlighted well.