Biggest two off the top of my head is poor quality and lack of advertisement.



Why should someone pay to see either a bad story, poor production or bad acting when for the same $10 you can see a movie with an actor you generally like and a high quality production. Story may not be good, but still...



Then bad advertising. Nobody is going to see a movie they don't even know exists. Takes a pretty penny or the luckiest guerilla/social media marketing campaign in the world to compete with the big boys who spend hundreds of millions to make sure you hear about it on the radio, see it on TV, trailers before other big budget movies, magazine and print ads, billboards, etc...



Come to think of it, the successful independents might have a similar percentage ROI. A $60 mil movie might gross $600 mil and the $50,000 movie might make $500,000. Then it's a case of the more you put in, the more you get out.