Yeah, DMC4 was just an introduction to that big potential, but i think Itsuno has to make a decision for DMC5: Dante or Nero, because putting them again in one story mode will just limite both of them like happened to Nero in DMC4.
Actually, my strongly held opinion is that the best possible thing for them to do is abandon the idea of a linear "story mode" altogether. Have the game take place out of the Devil Never Cry shop so that, rather than taking on twenty chapters, you take on a much greater number of much smaller missions.
This would carry a great deal of advantages:
1) Deemphasizing campaign design and Uncharted/GoW-style "wow moments" would allow for a stronger focus on core combat and game design.
2) Much greater ability for the designers to tune the game's difficulty, because you could create a *single encounter* that is really hard to survive instead of having to worry about structuring an entire chapter that way. Think of the way you can select DmC's secret missions from a menu, or Bayonetta 1/2's Lost Chapter and Rodin fights. This would also drastically improve the score-attack side of the game (again, think of the way that Bayonetta gives you a medal grade on individual encounters instead of solely at chapter's end). Bite-size gameplay is great for a number of reasons.
3) This would make it possible to have a greater selection of characters available because, outside of a select few missions dealing with the core story of the game, it'd be really easy just to have Trish play mission 40, have Dante play mission 47, have Nero play mission 63, et cetera. DMC4's design says "only Dante plays this level; only Vergil plays this level." DMC3SE's design is somewhat superior in the sense that every level can be played with both characters, but it's flawed in that two separate save files are required. DMC5 is totally capable of blowing both of those out of the water with the mission-shop approach.
4) The ability for designers to reuse the same area multiple times for different missions would save some money without feeling offensive or cheap the way that DMC4's several chapters in a row of backtracking felt.
5) The game would much more readily support DLC and/or post-release support with downloadable missions, downloadable weapons, and maybe even a downloadable full character or two.
DMC5 is obviously preferable but a series reboot is still on the table.
I think what I just described feels like it'd reboot some of what feels archaic about the game (namely, the linear chapter-based design) while being able to naturally transition the story forward from DMC4 and actually giving us our first real playable sight of a devil-hunting team operating out of Dante's shop.
This is a touchy subject for some folks, but what DMC needs is sort of an RE4-style reboot of certain outdated game design concepts (while, in this case, retaining the essential deep combat and score-attack stuff), not resetting the story back to zero (it's a pretty damn simple story anyway).
I still find it weird that DmC 'rebooted' precisely everything that didn't really need rebooting while leaving all of the stuff that was actually a problem for the series in place.