I'm all for photorealism in DMC 5. While the style sounds like it'd be at odds with DMC's legendary hyper-ridiculousness on paper, from the E3 trailer alone the decision looks like it'll be a good fit.
Art direction notwithstanding, I think the human character models in DMC games in general have been fairly realistic, at least to the extent of the technology available at the time of development. So I trust this will pay off. Naturally, the developers can take more creative liberties with the fantastical elements - and I hope they do. DMC has always prided itself on some truly wacky enemy designs, and I expect nothing less this time around.
If you ask me, I'd love to see some enemies with body horror, BDSM, and religious influences. The kind of thing that would make Clive Barker or Wayne Barlowe proud. And the disgusting "organic" architecture reminiscent of the Leviathan level from DMC 3 and some of the later missions in DMC 1 needs to make a return. A great example of that kind of environmental design was in EA's Dante's Inferno game, which was waaaaayyy better than it had any right to be.
But I digress. I have full faith that modern technology and realistic graphics will do the timeless over-the-top spirit of DMC justice.