I would say that a campaign in the ALIEN RPG could do fine without the xenomorphs. There are several other core themes within the franchise. Personally, I would prefer to include the xenomorphs in some way. Perhaps without the usual violent confrontation on a spaceship or in a remote colony... I would like to make it new in some way. It might, for example, be interesting if they were in background with some other drama around them.
I have already tried to grasp what the game (and the entire franchise is all about) . Here is a slightly edited version of my earlier post. Perhaps you could skip the third answer (I just tried to think a bit out of the box). The thematic core is, at least to some extent, a matter of interpretation.
What is the ALIEN setting really about? Well, dangerous xenomorphs is the most obvious answer. They are there in all films, for sure. But what they really are is not that certain. They seem to be able to come in many forms and sizes, some propably totally different from what is known so far. Maybe in the form of bizarre fish living in water (or other liquids) or as tiny but dangerous insects? Or maybe some kind of biomechanical microbes? What if they did something else than kill everyone around them? Building a huge nest? Contacting other beings somewhere else?
Another answer to the initial question, is that the setting is really about the Weyland Yutani, a huge capitalist corporation willing to risk anything to gain more power and knowledge. To me, The Company is actually more interesting than the xenomorphs. Quite early on, I would like to see the Company representatives in action. They should have a large and complicated agenda, including stuff that is not entirely visible, at least not from the start. They must know a lot, some stuff that is even hard to imagine. Getting a glimpse of that early on could be really cool. The scenario should feel like a small piece of something much bigger. A huge, dark unknown.
A third answer to the initial question: the setting is about Ellen Ripley. She is, in some form, the main hero in four of the movies. It would simply feel very ALIEN to make her a part of the game. The PCs might get a message from her: she might want to know something or get something fixed. Perhaps she has recieved signals from a distant moon or unknown ship or so... Another angle might be to make Ripley herself a playable character during a mission. She doesn't really seem to like Weyland Yutani. Maybe they just want to use her after some earlier incident. It may also be cool to see her as a potential enemy, maybe as leader for a rival crew. That would be a quite surprising opening of the game. And of course, she is also a person of interest for many. Who was she really? Why was she really on NOSTROMO in the first place? What did she know? Who knew her? Those questions can be relevant during a very long time frame... The same goes for her daughter, Amanda Ripley, the main character in ALIEN ISOLATION.
A fourth answer: the setting is about exploring the unknown. There is something strange out there – xenomorphs, Engineers and perhaps other stuff too. I can imagine there must some really wild and strange planets, asteroids or abandoned space ships (full of living plants, 5000 years old...). The Corporation (and others) probably wants to know more about this stuff. Or they may already know a lot... One initial discovery might lead to further investigations...
A fifth answer: the setting is about humans who interact with synthetics (a k a "artificial persons"). This might be a theme that is not fully visible from the start (or maybe it does), but after some time it gets obvious. The synthetics usually follow a very strict and secret agenda. Their presence is usually tightly connected to The Weyland Yutani Corporation; in a sense they are personal incarnations of The Company. But there are, of course, some problems. How independent can synthetics be? Do they have some kind of emotions? Should they just follow orders? What are their deepest motivations? How are they affected by their creators? What happens when (if) they take part in a large rebellion? The synthetics are a key part of the ALIEN universe, just as important as humans and xenomorphs. They have long a history within the setting, reflecting larger conflicts and ideological tensions. In a way, they are constantly dealing with their capitalist creators (Peter Weyland and others), without them they wouldn't exist.
A sixth answer, that include everything I mentioned above: the setting is about everything we see in the movies. That might seem so obvious that it´s not even worth mentioning. I think it is. In fact, many of the events in the movies are so dramatic and important that they must influence a lot of other people, for example the leaders at the Weyland Yutani Lunar head quarter. When they (and others) get new information about the sensational xenomorphs they will probably do something: send new ships to distant locations, look for other lost expeditions, protect their new knowledge, start new research projects etc. The events in the films are just a part of a much bigger drama, involving other companies, factions, planets, and even beings. It´s all a huge story, involving all the stuff that makes this setting specific, and not just dark space sci fi with Lovecraftian creatures.