"Your mission, should you choose to accept it..."
I tend to start PCs out in the employ of an organization, be it political (a kingdom, a secret agency) or mercantile (a spelljammer ship, a mercenary company) and then have something awful happen to their organization within the first few sessions, so they have to either rescue it from the ashes or go off on their own.
So far, the players have almost always tried to rescue their organization from the ashes.
Once in a blue moon, they even succeed...
Once the game gets rolling, though, it usually bounces from one PC-caused disaster to another as the characters flee the consequences of their monumental, catastrophic, uproarious missteps. I've never had a d20 game that didn't involve one or more of: crashing one or more ships (often expensive, high-tech or magical ones; sometimes one of each!), burning a town to the ground (once, a major metropolis!), accidentally destroying the PCs' own organization, getting captured by a series of comically improbable missteps, or becoming involved in a land war in Asia.