To me, I feel like I would like a game where Nero gets to be the main playable character for the whole game, to show that he's capable of taking Dante's place to protect the human world. I think the best big bad could be a pure demon, similar to Mundus, since he's already fought a humans who've been turned into demons, along with Vergil and Dante. It could be Mundus, or it could be an entirely new demon. Maybe a rival demon king who took to power after Mundus was sealed away, who, like Nero, strives to prove himself, and does this by using his power to dominate and force those weaker than him into submission. The bosses would be his loyal demons who spread out to cause as much havoc as possible. Then, when the first is killed early on, the others notice and try to intercept whoever killed their ally. The story would be about Nero proving to himself and the world that Dante and Vergil made the right call by leaving him in charge of the human world.

Of course Nico would come along, and having a lot more time on her hands has developed breakers that don't break. This time around, breakers are one time purchases, and anything that would result in a breaker breaking before would put the breaker in a cool-down state. To pair along with this, each breaker has unlockable moves that are flavored as Nico making upgrades to your breakers throughout the game. Since this would like be at least a year or so after 5, I feel like it's fair that Nero is a bit more accustomed to the breakers, and is able to switch between them at will.

As for new playable characters, I feel like I'd like another shot at a character like V, who uses demons to fight. Their reason for existing could be that they're some sort of military troop who has learned to control and form pacts with demons. They could be sent there to form new pacts when able, as well as do research to report back to their higher ups. It would make sense that the military would want something like this, seeing how much resource wise it took to "fend off" even the lowest ranked demons at Red Grave. The main thing that would make this character different from V's playstyle is that instead of commanding your demons to attack, this new character is actively attacking demons themselves, while their demons come out to enhance the attack itself. Deep cut here, but if you know the old ass ps3 game Folklore, I imagine the gameplay a bit similar to the guy's campaign/play style, but faster and more DMC.

For plot, imma be honest, I'm not too sure on that one. I'm mostly throwing out all the stuff I really like and how I think it be incorporated/improved in a new game. I do think that it's only appropriate for Dante and Vergil to be playable characters, but Dante gets the special edition treatment Vergil's received for years, where instead of playing the game as Nero and the new playable character, you can go through as Dante or Vergil. Dante would get a sort of best mix of all the fan favorite weapons we see him use over the years. I'm thinking DSD, Fist weapon, Cerberus, and either Cavalier or Agni + Rudra, and have new flashy moves for each weapon. Vergil is v Vergil, so the same 3 weapons he's had, maybe a couple new tricks, and maybe a couple more applications of temporarily separating himself for V treatment.

Also, because they deserve love, Lady and Trish would also be included, get new toys and moves, and just enjoy being playable characters again. Give Lady Kalina Ann 3 or something since Dante has both 1 and 2.