Count me as one of those annoying The Wire fanboys. For me, the show's biggest flaw was that it ended too soon. Everything about the show was unbelievably great - the writing, the acting, the direction, the production - everything.
Three things struck me when watching the final series -
1. The Wire reminded me a bit of Lost in that you were made to work for your viewing pleasure, it wasn't all laid out with an idiots guide to plot points. As a viewer, you ended up rewarding yourself whenever you figured something out or spotted a particular nuance and then gave yourself a metaphorical pat on the back.
2. The cyclical nature of the characters and the blurring between good and evil and how the streets / institutions crush the human spirit. Carcetti becoming Royce, Michael becoming Marlow, Duquan becoming Bubbles, etc.
3. The general unease / excitement created by the doctrine of killing characters off. Just when you got safe and settled and thought, 'ah, he's going to do that', someone in a hooded top would walk up and shoot them in the head. This constant background tension added greatly to the drama.
Oh yeah, and loads of N-words were getting capped in their asses for dissing and shit.