If they do make a Devil May Cry 5 (and hopefully DmC2 alongside it) then it would have to do a lot of explaining to bridge Devil May Cry 4 to Devil May Cry 2, among other things.
For one, it would need to explain Nero's existence. Whether he's Vergill's son or not, we need closure. Also, I'd like to see the story flesh him out more and not make him simply "Dante 2.0." Give him a unique personality that separates him and Dante. It would be nice to see two protagonists who contrast one another in interesting ways. It could provide some great banter between the two of them. Speaking of which, it would be cool to see Nero working alongside Trish, Lady, and Dante at Devil May Cry, hunting down monsters and kicking ass in general. It would also be fitting for Nero and Kyrie to be crashing at Dante's place after their Order of the Sword woes.
Moving onto Dante, I'd say that we should keep him as he was in Devil May Cry 4. I loved his personality in that game and feel like it epitomizes him. The same way DmC Dante is defined through his gritty but coy swagger, our old pal Uncle Dante was defined by his carefree personality, the ability to laugh in the face of great evil, but also a genuine admiration of humanity. Also, he HAS to be voiced by Reuben Langdon once again!
Where the story itself would go, I couldn't say, and what sort of threat the devil hunters would face is even harder to predict. The main conflict would have to include an interesting villain, someone who at least rivals Mundus and Vergil. I'm sorry to say, but The Savior was a bit underwhelming.
Kyrie should return and also play a larger role that exceeds getting kidnapped. She should be there for Nero in his when he is in need of wisdom. She'd help him with tough decisions and also comfort him in times of anxiety. I'm sure someone else said this, but it would be cool to see her beginning to be trained by Lady and Trish to defend herself against demons, especially considering the sorts of people she hangs out with. Also, there is potential in exploring how she feels after her brother, Credo, died. Lady should also return, but more than a cameo like in Devil May Cry 4. I want to see her kicking ass with everyone else, damn it! Same goes for Trish.
More importantly, the characters should go interesting places and give us reasons to care about them, so for Dante and Nero, I had an idea for two very specific character arcs.
After Devil May Cry 4, Nero is struggling with his identity and becomes more and more curious about his heritage. Dante of course, knows the truth: Nero is Vergil's illegitimate child. Dante still feels guilty about his conflicts with Vergil/Nelo Angelo and simply wants to bury his memories of those unfortunate occasions. This isn't helped by the fact that Nero is investigating his connection with Yamato, which was once used by Dante's brother. When Nero discovers who once wielded the sword, he pesters Dante throughout most of the campaign of who Vergil was, and why his sword miraculously came into Nero's possession by chance. As I said earlier, Dante doesn't wish to confront his inner demons that are brought out when he thinks of Vergil. There's still some serious guilt there. This would serve as the two major story arcs of the game. Two protagonists are examining their pasts. Nero is discovering his demons; Dante is remembering them. At the ends of the game, once the potentially world breaking conflict is resolved, Dante finally talks with Nero. He tells him that he's been taking care of him because he's Nero's uncle, and Vergil was his father. He tells him that Vergil was killed at his hands and his guilt prevented him from telling him the full truth. Nero, after spending time contemplating, decides to accept this as truth and continues to wield his father's blade, claiming that the innocent blood on it will be avenged and that he will use Yamato far wiser than Vergil ever did. Now these two characters have matured and changed by the end of the game in more ways than one. This story arc can also help build suspense. Since Nero is Vergil's son, we don't know if he'll react maturely to the discovery of his heritage. He could flip out and go against Dante and possibly lash his anger out on the world. This weighs heavier on Dante's indecision.
Concerning gameplay, I'd like to see Nero as well as Dante be playable characters throughout, although I would hope that we wouldn't be forced to play as either character and each of character has their own maps and bosses. Also, I wouldn't mind the inclusion of a city hub where you can visit Devil May Cry as either Dante or Nero and get side missions, and also purchase upgrades and items from shops and store vendors.
Well, I typed out a lot more than I had intended and rambled here and there. Sorry about that! I'm also too tired to check for spelling and grammar mistakes, so I hope there aren't too many. Personally, whether Capcom makes DMC5 my way or another, there are so many possibilities floating around that it makes me excited to think of what others will come up with in contrast to my thoughts.