Blade Runner is my favourite film, and I am looking forward to the sequel with great anticipation.
I am also a big fan of Alien AND Prometheus, and I hope that they go the exact same route with Blade Runner : Use the same universe, but make it an almost totally unrelated story.
I think the problem with Prometheus is that it was too heavily marketed as a direct prequel to Alien, when in fact the two movies should never even be compared to one another, as they are such different beasts. To me, it was the best science-fiction film of the last fifteen years at least, although this year's Under the Skin is now at least on par with it, maybe even a little better.
Like all good Science Fiction stories, Prometheus is more concerned with ideas rather than plot, and it is much more interested in what it has to suggest than what it is actually saying. As far as I'm concerned, the first Blade Runner is guilty of the same thing, and following that route is again the way to go with the sequel.
I only hope that Ridley Scott and his screenwriter(s) resist the urge and public pressure to make this a direct sequel. There can be no direct sequel to Blade Runner, only a thematically linked movie set in the same grandiose visual universe.