Hmmm... let's see how many I can think of on the fly...
Here's one.
The year is 3626, and Humanity is at war. Allied with hundreds of other alien races, Humanity was and still is what was once a great alliance of races, defending against a huge extra-galactic empire, named the Isshar. They fought for 200 years, but system by system, planet by planet, many of the races that were in the alliance have become extinct, or severely reduced. Almost all homeworlds have been glassed or outright destroyed, with Earth is on it's way. The Isshar have already reached the military system of Sirius (which, in case you are too lazy to look up in wikipedia, is the
5th closest star to Sol), and have severely battered almost all defenders. Nearly all other nearby systems were not prepared for the war coming this close, and only have basic defenses. In addition, our seventh through second fleets are gone and our first is almost unfit for fighting. All we can do is fight a guerrilla war, and evacuate. The players play the role of special forces that fly on the UESF (United Earth Special Forces) Raptor class Destroyer
Ballista, fighting quick engagements against many Isshar installations and extracting VIPs or other important things like prototype weapons, armors, shields... The players will have very little support throughout the game (the Ballista is hardly enough to even go against an Isshar Frigate, and it'd come out severely damaged. In addition, the Ballista was not designed for troop transport, so it contains little space for personnel, so the players get little friendlies.), and each time they go somewhere they should have very little time to lollygag about before they start getting into trouble.
Pros:
Gritty storyline, giving players a sense of doing as much damage as they can for the sake of humanity, possibly committing suicide.
Futuristic, do whatever you want with technology.
Players have little time to mess about, and thus will do their damn missions.
Players can do alien races, but are encouraged to do humans (you should have a bit of raciest dialog if the majority of players are alien for flavor).
Players will have to protect their main ship, the Ballista, and care for it. Anti-ship gun shooting at it? Destroy it or you're stuck on the planet! It took a salvo in the FTL engine and can't activate or repair it? Gonna have to steal a replacement.
Planets can be in any number of states: Fine, evacuating, under attack, being glassed, or being destroyed. Pretty much whatever you want.
Late in the future, many technologies can be put in with reasonable believability.
Enemies more advanced than players. Players are encouraged to try out new technology. Whether or not they can figure out to use them is up to a dice roll maybe?
Cons:
Sci-fi, meaning magic needs some tweaking in order for it to make any sense in the game.
If you're not used to making your players fear death, then this may be hard to GM the way it's supposed to be (AKA, players need to be careful). If it's not hard enough, players won't feel a sense of danger for them and humanity throughout the game.
Kinda a sort of "This should be GM'd this way" sort of idea but... well, sorry, I just can't help myself, and I have a headache or fever right now, and it's pretty late, so am not at 100% full mental capacity right now.