I always wanted to make a space mod for Fallout 3, I imagined that, the G.E.C.K., while powerful was never able to fully repair the earth, and of those that existed, only a few select areas would be restored. Cut to 500 or so years later. Humanity has mostly regained it's foothold. Much of the earth is still barren waste, but alternate sources of power and food have been found. Many people live in giant walled cities, kind of like the PITT, but more built up and industrialised.
There would be a number of state like entities that shared power in the world, more like corporations than true governments, but holding the population centers together nicely. At that point, earth has becoming especially overcrowded, with little respite in sight. It is then that man finally reaches back into space. Combining derelict alien technology and their own technological know-how, massive colony ships are created, each with enough space to house 20,000 sleeping colonists and an active crew of about a 100. Including a small military force staffed by regular humans and improved Super-Mutants (The FEV process doesn't create as much disfigurement or mental damage after having been perfected.)
Applicants are selected at random, and while the ships are set on course in the general direction of a possible habitable planet, this is no guarantee, and the ships could very well end up floating coffins.
The game itself, would basically be Fallout: IN SPAAAAACE! But would keep the same generally run-down makeshift tone, and provide a more compact area in which to explore. You would play as a nameless (well you'd name them) tech aboard one such colony ship. More focus would be put on the interactions between the crew and various factions on board, and you could have a chance to join one of these, i.e. the military, engineers, science, obligatory rogue faction.
The plot would take place over 4 years. As there would be a period of sleep for the active crew-memebers in which they're placed into stasis. There would also be a group of non-crew members who, because they didn't make the sleeper selection process, were allowed to come aboard and live in a small 'township' where they maintain the hydroponics area and stay awake to alert the crew of any problems. That way, since you as a character have your own stasis pod, you can get to know the non-sleeper crew, and even watch them age and see their attitudes change depending on how events play out on the ship and how you interact with them.
Of course, while the bulk of the missions would take place aboard the ship, and relate to your own duties. There would be plenty of opportunities to get off ship, including bits were you may encounter derelict ships, even the remains of a failed colony ship or too, or encounters with aliens or other anomalies. Till eventually and hopefully the ship reaches it's destination. Which, it may not depending on the events of the preceding four years. You may end up at the wrong planet, caught in a gravity well, have the ship destroyed through sabotage or even have it conquered by aliens.
Ideally though, it would end with the Colonists reaching their new home. And promptly nuking themselves. Ron Perlman pops up at that point to deliver his classic line.
You know...I'm wondering if all that doesn't sound like Fallout anymore? Didn't mean to pull a 2K there. xD