You may need to try a lot of different approaches until you find something that works for you. I think Ceosol's approach is a good one--I've done that before.
My usual approach, though, is different. I start with an experience I want the reader/player/etc. to have. (This doesn't have to be the ending, BTW) A key component of a good story is to make it and its characters believable. What would put the character in their particular position? What are their motivations? What about their world is influencing them? Basically, I'm building a character up, and the story comes out of the explanations for why they are the way they are and why they are in the situation they're in.