And, unless they somehow account for how Deckard the replicant has grown old
... I just don't see how they get there at all. He's not just a hunter of them, he is one.
So either they start this one in which Deckard isn't a replicant, and they'll piss off the fans of the movie. Or they'll have to treat very carefully to explain it.
Of course, there is an easy way around this.. just because it is now 30+ years after the release of Blade Runner, doesn't mean that this amount of time has passed in that world. Deckard could only be 3 years older, and be deteriorating rapidly.