I don't see them rebooting the series again. I feel like after last time, that must feel like dangerous territory for Capcom.
So I think a DMC6 is more likely. As for Nero being the lead. Look, we all know he wasn't popular when he got introduced in DMC4. Ironically though, it was DmC that started to warm the fanbase up to him. Back then, there were a lot of posts in the veins of "Oh nevermind, I'm sorry Nero, I want you back now", and I always thought that was kind of a knee jerk reaction to DmC Dante and stuff. However once DMC5 came out, I dunno, interacting with other fans I got the decisive impression their general opinion on him genuinely flipped. Felt like fans generally were pretty pleased to see him back and they actually liked him now.
I think people's positive reaction to Nero returning proves that he can be the protagonist. The question is, without any Dante at all? I think yeah, it's time to retire the guy. The ending of DMC5 sets up his passing of the torch to Nero and that's fine. Personally, I'd like a DMC6 with Nero as the sole protagonist, with his own side cast (Nico was already a W on that front, she was received very well), and possibly Dante being relegated to a DLC that shows what he's being up to in the underworld with his bro.
Could Capcom do a Sparda game instead? I can see them go that route though honestly, I wouldn't want them to. Not because of fear that they wouldn't do it justice, but simply because I'm tired enough of hearing about the times of his deeds, I don't wanna play through it too. I once would have been excited about a Sparda game, now, not so much anymore. I'd still play it, but, eh, I'd prefer focusing on the future.