For my upcoming space opera campaign (which starts tomorrow!), I've decided to hew pretty close to Star Wars——which is, after all, the defining modern example of the genre. So, the game will be set in a galaxy with no mention of Earth at all, and the aliens will generally be more "alien" than your humans-with-bumpy-foreheads variety.
I've named this setting the "Primus Galaxy", so-called because it's the only known inhabited one——other galaxies have been observed by astronomers from Primus, but they're not reachable with current FTL technology (which I'll get into with my next post). Unlike the Star Wars galaxy, Primus is by no means well-explored. Instead, "Known Space" consists of a relatively modest stretch of territory in one of the middle spiral arms, maybe 10,000 light-years across. Within Known Space, there are three major political entities, "great powers" jockeying for supremacy. Everything beyond it is "the Unknown Reaches", with a narrow band of Borderlands in between.
The three Great Powers are the Federation of Man; the Fleen Consortium; and the Vulgh Empire. They're all, to a certain extent, "evil empires" in the space operatic sense: oppressive, dictatorial, and not apt to be friendly toward a band of adventuring rogues.
(1) The Federation of Man is the center of the campaign, a kind of feudal state where regions of many star systems are ruled by counts and princes, all beholden to a single High King. The High King, meanwhile, keeps his vassals in line with secret police, spy networks, etc. The humans have slowly expanded their territory out from the core worlds, absorbing alien cultures into the Federation where they encounter them, generally under the pretense of alliance rather than conquest.
(2) The Fleen Consortium is ruled by a race of "Roswell Gray" type aliens, who also happen to be chiefly concerned with trade, finance, and profit. Think Ferengis, but without the comic relief or the anvilicious aesop. Their society is an Orwellian corporate dystopia, with mega-corporations (rather than a government) openly running things in the name of self-interest. One of the major sources of profit for the Fleen: as an ancient, scientifically advanced, and naturally psionic species, they hold the monopoly on "psychic surgery", the only means by which a non-psionic individual can become psionic.
(3) The Vulgh Empire is the most overtly violent and antagonistic of the lot. The Vulgh are over-sized reptiles with a warrior culture, an unquenchable blood-lust, and a mysteriously occult religion that seems to drive their conquests and expansions. The Vulgh Empire sits between the core of the galaxy and the adjacent territories of the Humans and the Fleen (who have become grudging allies in the face of the Vulgh threat). Otherwise, very little is known about the Vulgh, except that they're as likely to obliterate a planet as enslave it.
(4) Rumors also persist, especially in the Federation, of a "fourth power", a distant lost civilization which has eluded the grasp of tyranny and remained a free nation among far-off stars. Most likely, though, these are just stories invented by various rebel groups and isolated resistance movements, circulated to keep up morale in the face of overwhelming odds.
This is the environment in which my players' characters are about to find themselves tomorrow. And while there are a number of dangling plot threads just waiting to be snatched up, they all lead in quite different directions: a galaxy is the best sandbox setting one could hope for. At this point, I honestly have no idea what the PCs will decide to do, once the action kicks off and throws the party together. But there will indeed be a "crisis moment" at the beginning of the campaign, a situation that forces the players to work together to come out of it alive. Is that artificial? Less so, I believe, than "you all meet in a bar, spend the afternoon drinking together, and decide to risk your lives for each other."