Here's one- I really hate the over-use of creepy children in all horror mediums, so you could subvert it. The main character could be one of those grown up, their parents disappeared and they grew up orphan or passed around the family. They either
1) Got really successful in life, and then something from their creepy childhood comes back to mess it up. Or
2) Turned into an alcoholic from what had happened, and then has to deal with their conscience.
In my opinion 1 would be a more interesting and less cliched film, but 2 would give more potential to investigate the 'human condition' which makes great horror.