When?
One of the key issue will be to situate the new storylines, both in space and time.
From a storytelling standpoint, Alien did not make xenomorphs the target of the Nostromo’s crew. The goal of the Nostromo’s crew was to satisfy, reluctantly, a call for help, a distress signal. While attempting to do that, the crew would stumble upon xenomorphs and Hell would open wide.
This kind of scenario follows an extremely common pattern, where protagonists are tasked with a mission that tears them apart or unites them in the face of an implacable force. Said protagonists go about accomplishing their mundane endeavor and something goes wrong. Eventually, tension develops, then despair. A climactic conclusion usually involves the complete destruction of the antagonist.
Aliens, on the other hand, played with a different subconscious paranoia. Aliens used the following themes: The Evil Corporation, Greed, Overconfidence in Military Force, Distrust of the Unknown, Instinct Above Duty.
Yet, the official Search and Rescue mission goes wrong and Hell once again opens wide.
What strikes me is that both Alien and Aliens were as much about human interrelations than human vs. xenomorph survival.
In both movies, xenomorphs would bring out the best and the worse in human protagonists, as if these great qualities and flaws were waiting to be unleashed.
I digress.
I would not base any future Alien-derived game on any material beside Alien and Aliens.
I would preserve the same narrative pattern, where a mundane series of tasks leads to a dramatic and extraordinary confrontation with xenormorphs.
I would exploit all past paranoias and also leverage paranoias of our time. (Annihilation by Consumerism, Dehumanization, Self-destructive Isolation, The Enemy Within, Outsourcing)
I would connect any new storyline to Alien and Aliens, in some ways, but without obligation.
I would focus on what happened between the time the Terraforming Colony discovered the egg chamber and the time when LV-426 was destroyed. To take the action away from LV-426, to create a parallel storyline, with separate characters, in a different environment.