I actually just started a campaign just like that! Centred around a ~25-man gang, mainly members of a couple of ork families who got together to protect their neighbourhood against Humanis and the such. The PCs are parts of the main family or of the gang, or closely involved (love interests and such).
Lots of the starting-level trouble will be things like other gangs making moves against the "211th Street Bleeders" (gotta love that name, one of the players made that and the families and gang up, gave me great stuff to work with), people dealing drugs on the wrong side of the street, family members getting into trouble. Not running, per se, but probably building up to it in the end.
The important thing is to centre the action around things that the characters are interested in, so that you donīt have to force them aboard the Plot Bus ("Itīs meant to take you where the plot is!"). The players must be willing to write a lot of character-stuff for you to build on for this, though. And not just give you a list of stats and gear...