I've been a Simpsons fan ever since the first episodes aired back in 89/90. Like most comments I agree that the show has lost a lot of it's quality and popularity in recent years. While sets based on the show would have some popularity, I doubt that they would be top sellers like some of the other franchises and would likely end up as discounted parts packs.
However, what I could see happening is LEGO producing Simpsons minifigures that would be included in special "collector" editions or even regular editions of the DVDs. rather than being marketed strictly as toys.