When it comes to the main Alien series, we have come to an end-pass thanks to the mess of Alien Resurrection. The fourth film was basically the swan song of the series and Sigourney Weaver's portrayal of Ripley. Weaver made it clear she was against the xenomorphs reaching Earth in Resurrection. The studio agreed and cut a bunch of the original third act Earth scenes out of the film. But Fox would later go on to make two horrible AVP films that explored that premise. Fox would need to sadly move away from Ellen Ripley for a compelling sequel.
Prometheus was an excellent addition to the Alien universe and could very well lead to it's own series of films. We already know that Prometheus 2/Paradise has a completed script from Jack Paglen (Transcendence) and very well could be the next directorial effort from Ridley Scott. This of course could be officially announced when Ridley finishes post-production on Exodus. As the director has all but confirmed Prometheus 2 is next for him.
Granted, Prometheus 2 could jump-start new movies if the film's concept lends to more stories being told, but it's possible they will end at two features. As Prometheus (originally titled Alien Origins) was intended to be made in two parts but the studio decided on making one. In the hopes to gauge audience demand for a second installment. These movies are set 20 years before the events of the first Alien, and by the end of them will likely tie-in into the events of LV-426 (which was the original plan from it's conception).
One way to continue the main Alien franchise is to make a standalone feature. Not to say something that needs sequels but could be a one-off installment within that universe. It was recently announced by Sega that they will be releasing a new Alien game in late 2014. The awesome catch is that Alien: Isolation is based on an original idea, and will focus on Ripley's daughter Amanda. It's being closely put together with the help of the studio, which provided a ton of materials from the original film. The studio is making a live-action Assassin's Creed movie, they might as well adapt a video game property they already own.
The game focuses on Ripley's daughter fifteen years after her mother's disappearance, and is sent to a space station in the hopes to find answers about her mother. Only to find that a xenomorph is aboard the station and the horror begins from there. Besides that, there is little known about the plot. Amanda is employed by the company (Samuels) and seeming is on her own in the game. As much as I want to see Weaver back, continuing the franchise post-Resurrection is a bad idea. Having this new character take her place wouldn't be the worse thing.
Amanda Ripley-McClaren is a canon character (unlike Shaw) and was introduced in James Cameron's Aliens (director's cut). She could make an excellent protagonist and a reasonable way to continue the Ripley name without Weaver or a reboot. I wouldn't mind events from Prometheus leaking into this film as well. Explaining where the aliens come from and if they're on any other planets surveyed by the company. We got the impression that the company knew about the xenomorphs from the get-go which makes Prometheus plausible, having Amanda caught up in similar events also wouldn't be a stretch.
In the director's cut of Aliens we find out that Amanda has died before Ripley was rescued by a salvage crew. It's possible Carter Burke was either telling the truth or actually lied about her death, allowing him to manipulate Ellen later on. Putting into question Amanda's actual fate. We know it's not out the question to have a company member hide information or exploit people to get what they want.
It's revealed that Burke sent out Newt's parents out to check out the Space Jockey ship leading to the entire colony at Hadley's Hope on LV-426 getting wiped out. He was also planning to sabotage cryotubes on the way home, after setting loose face-huggers on Ripley and Newt. Essentially capable of killing a massive amount of people to get a hold of the xenomorph as a weapon. Lying about Amanda's death or not revealing a previous company mission would be in Burke's wheelhouse. This ruthlessness is a running theme with characters from the company, and I'd love to see another slime-ball (Samuels?) try to talk Amanda into unknowingly taking-on a suicide mission.
So how does Amanda bump into a new xenomorph fifteen years later? That's a great question which hasn't been revealed by Sega, but I would assume that this space station perhaps discovered the one Ripley launched into space in Alien. We've come to understand that they're tough sons-of-bitches and might be able to handle the vacuum of space and could survive it (even for years).
LV-426 might come into play again as the company does eventually colonize the planet, there has to be a point when another ship discovers the beacon or the alien ship. There is also the possibility that LV-426 might not be the only planet with xenomorph eggs on it.
In Prometheus, they sort of setup the idea that LV-223 could end up becoming a ticking time-bomb, with a large supply of black goo still there and a xenomorph-like creature walking around. There are assumptions that the black goo is meant for Earth, but never explained if the Jockeys wanted to turn humans into zombies like Fifield or something else. However, I do expect Weyland Industries will want answers about LV-223 and could send another team out there (possibly rescue or military in nature). This leaves a lot of windows open for Amanda to discover other dangerous things in the Alien universe.
Australian actress Rose Byrne has a striking resemblance to Amanda on the cover of this box art for the game. Rose has been apart more than a few Fox films such as Sunshine, 28 Weeks Later, and X-Men First Class. It doesn't hurt that she's had roles opposite Prometheus' Michael Fassbender, Idris Elba, Patrick Wilson and Rafe Spall. She could easily be mistaken for Sigourney's daughter making her a believable candidate to play Amanda.
When it comes to a director I can't say I have many names in mind besides Duncan Jones (Source Code, Warcraft). He proved with Moon he can could build a realistic analog science fiction film and do on a strict budget. The film was also an obvious homage to Alien and I can't think of better director that could re-energize the franchise like Duncan could. Jones is also a self-proclaimed video game junkie, so I'm sure he's intrigued about Alien: Isolation like the rest of us. Duncan is also a writer and could give a lot of credibility to the project with his input as a fan and filmmaker.