Yeah but if some of the Deus Ex 1 elements start to become dominant then it'll get progressively harder for them to tell a fresh story, at least for people familiar with the canon. I think one of the reasons HR works so well - and why making it a prequel was a good idea - is it basically tells a brand new story but keeps it in the same setting. If UNATCO for example is a dominant part of the next game, which I would fully expect, I don't know how interesting they can make them for the Deus Ex 1 players who already know what they're all about. There's no real mystery to them.
One cool direction they can and basically have to go is the progression from mechanical to nano-augs, which should be interesting to see. I assume that's at least one of the major themes the next game will concern itself with.