Heathers?

Blood Simple is one that I dont think has been mentioned yet.

I considered Slacker (after all... it inspired Kevin Smith to make films), but I think Clerks had a bigger impact on cinema.

Pink Flamingos

Empire Strikes Back is an independant film.

But it wasn't nearly as influential as Star Wars.

Ditto. Is it still the most financially sucessful independent movie? It was for years. Blair Witch was probably made for less but did it have as high a return on cost rate? Also Halloween was never picked up by a major distributor/studio. Started the trend of naming movies after a date(Friday the 13th, Prom Night, My Bloodly Valentine, April Fool's Day). Started the teenage body count/slasher trend which still goes on today.
Had to go look it up. Film was distibuted by the production company, Compass International Pictures, no major studio support.

Deep Throat?

With marketing, the budget was a little over $25 million. The film itself only cost $60,000. Took in $248 million worldwide making it the most successful Independent ever, at the time. No idea if something else has topped it.

Halloween budget: $325,000, $47 million take.

My Big Fat Greek Wedding took in $241 million domestic alone. Doesn't change the fact that I will never, ever see it.