I feel like the central problem to a Prometheus sequel is that which plagued the concept of an Alien prequel for years. Ridley's concept was to make a film centered on the Space Jockeys. He frustrated the idea because its damn near impossible to make an accessible film to audiences about Alien beings that don't feature humans themselves. Think about it, a film where creatures interact who do not speak a language that anyone can understand. A culture that is entirely beyond comprehension because of the nature of what it is. How can anyone, even someone as talented as Ridley Scott be expected to deliver a product that would revolve around that and STILL involve mainstream audiences.
He was sold on the Spaihts pitch because Jon found a way to make it a human story that bisected with the Jockey story. It certainly wasn't a groundbreaking idea; voyage into space, discovery of intelligent life, etc, but it worked in terms of getting the audience to relate to what was happening on screen. It became a story of man and much less a story of Engineers. We've now been teased that the next installment will be the story of the Engineers and the same problem still exists, how does Ridley make an engrossing and enthralling cinematic movie about a culture that has only tenuous roots to humanity?
So we're back to the notion that Ridley has to explain, maybe not fully, but on a much bigger canvas, has to explain and represent this Jockey race and craft a two hour plus motion picture around them and their culture. That's the territory he's boxed himself into, only in this occasion, there is a human and a robot to place the story around. The next script will truly have to be creative and ingenious to make the idea fly.