A couple of months ago, someone asked if I thought I would have recognized something with as much potential as Harry Potter, had it come across my desk as a submission. (Read post here.) Of course, I said I would...but it's not always clear cut.
I was browsing Nathan Bransford over the weekend and found his take on that. He said it better than I did. Go read it.
And while you're there, bookmark his blog or pick up his feed. He has great info and he's pretty funny too.