I took a Google Map of the actual neighborhood I live in and drew over it with the homes and businesses that exist in the SR universe version of the neighborhood -- including a warehouse, an auto shop, a bar, some low-income projects, etc. -- and am having a fixer & a fence, two brothers, decide to move into the area by buying the warehouse as the place they operate their business from and an apartment behind it to live in with their families.
The PCs are hired first to clear out the local gang so that its "their neighborhood", and then can go on any number of unrelated runs (where their fixer doesn't screw them over, since they need to keep working with him), mixed in with various missions to defend the neighborhood gangs trying to move in, do courier runs, deal with more sensitive territory issues relating to underworld elements, get hired by people in the neighborhood who have their own problems (they work for corps, they have families, they are members of humanis, they are sympathizers of the ork underground, etc), and so on. I think giving the runners a "home base" they feel the need to defend is powerful, and gives more weight to the need to keep notoriety low.
Well, that's my idea at least.