It is so hard to pick one with all of the great productions he has been involved in.
With that said, "Do the Right Thing" is my all time favorite. The camera shots, the various perspectives of the Brooklyn residents were very insightful. The soundtrack was masterful (especially the lead single "Fight The Power" by Public Enemy).
Spike also has a knack for not only using top rated actors, but also discovering quality talent, ie. John Toturo.