Easy... "Female Trouble". It's Waters' masterpiece and Divine's greatest tour-de-force. There's actually a great deal of thematic depth and true pathos, but all without undermining the trash/exploitation element.
Of his straight, mainstream films, I like "Hairspray". A good flick, but a pale reflection of the perverse glory of his earlier pictures.
I honestly can't pick a favorite. Polyester was the first Waters film I saw, so it holds a special place... The perversity of Desparate Living certainly appeals to me, though I wouldn't rank it was one of his best.
I have probably viewed Cecil Demented and Pecker more than any of his other works, and I love how they skewer the commercial film and art scenes respectively. Cecil has some of the best lines of his films:
I thought I would bump this thread for anybody who's online right now because if you go to Facebook right now, the Academy is livestreaming a 30th anniversary reunion panel for John Waters and the cast of Hairspray.
The Hairspray Q&A is now over but can still be played back on the Academy's Facebook page. It was a half hour long, preceding a screening of the film which is happening now at the Academy's theater, and was really fun and interesting to watch.