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I vote for THE WIRE, easily, and I'm a big Sopranos fan.
To the person above, Omar Little *was* based on a real guy. In fact I read in the New York Times that he recently married Fran Boyd, one of the three protagonists from THE CORNER (if you haven't seen it, get thee to Netflix immediately). Without Simon's HOMICIDE and Simon's/Burns's THE CORNER, there would be no THE WIRE. When Simon started as a journalist, I can't imagine he would end up where he is today, creating some of the most important art of the last 20 years.
When Season 3 of THE WIRE ended, I was sad. I felt like, as a suburban white guy with no history of trouble, that I was completely powerless to do anything to fix the problems that Simon, Burns, et al have laid out for us. My wife immediately found a great way to help here in Cincinnati - Crayons to Computers (an organization that collects donations for its "store" where inner city teachers can "shop"). We volunteered and will be going again next month. I don't know any other show that flat out makes you want to go out and try to change the world. All Sopranos does is make me want to order ziti.