There is no need to be afraid of the bumps in the night when you are those bumps...
Predators
The players are a group of shadowrunners who, for one reason or another, are not looked upon well by Shadowrunner society (let alone normal society). They have banded to gether to face the world and make their mark.
Prey
Since the characters operate out of the Redmond Barrens, they have to deal with the gangs that call it home. Add to that the need for some players to eat "someone" and the relationship quickly becomes tense.
Movers and Shakers
Some one has to pay a Shadowrunners bills and more often than not it's a corporation. Whether they are one of the Big Ten or a small fish looking to feed, they all have the money and the desire to pay someone to break those annoying laws that get in the way of business.
From the notable to the insane
When you commit crimes for a living you are bound to get on the wrong side of someone. You will also need friends and contacts to keep those people off your back. Then again, there are those poor people who get caught in the crossfire.
A timeline of shadowruns and murders.
Tell people you are running a game and tell them to be imaginative. A Ghoul, a Weretiger and a Vampire later and a plot starts to form....