The only major downside of NT's button set up is the fact that you need to hold the triggers to use some weapons that you might want to use constantly. Because that would mean you have to keep pressing the button nonestop, to the point where your fingers might hurt. But I'll also note that holding the triggers is usually nicer than holding any other type of button, and many games have done this before (like how you sprint in Prototype or how you aim in CoD).
Another thing would be dodging while in demon mode. RT is demon mode, and RB is used to dodge. I don't know why, but I've always had a hard time pressing corresponding triggers and bumpers at once. This reminds me of DMC3 whenever I built up my Trigger Bomb (the explosion thing you do when you go DT, I forgot what it was actually called) and when I tried to switch a gun using LT at the same time. That was a nightmare, I just couldn't do it. Either I would take too long to switch a gun (like a second, that's pretty long for a DMC game) or I would randomly burst out into DT and didn't hit anybody with it.
Otherwise, nice change of pace, I must say. Changing all these weapons on the fly without the need to cycling through them is a wish come true for me, I've always wanted Capcom to make a DMC where they had a control layout where I didn't have to cycle through things and keep track of what guns or weapons I was currently holding in order to get to the next one.
That brings up a good point though... what about the guns? We covered the weapons but we don't know how to switch between guns. Unless we have only two weapons in each mode and two guns/whips which makes a total of 6 weapons and 6 guns, and we switch guns by pressing up and down and weapons by pressing left and right on the D-pad... I don't know.
Btw, yes, I'm "new" but I've been lurking this forum for as long as DmC was announced XD