I used to GM from the perspective that the story I cooked up is everything, and the players are there to flesh it out (by being there). This resulted in many miserable failures for the reasons other posters elaborated upon in their own experiences.
I now try to make several (No less than 3) hooks that are essentially mini-adventures that ay or may not have potential to lead into a bigger story line. I Don't create a bigger storyline intended for the players until after the players have inhabited their characters for a few games. If you do so before that you run the risk of the characters/players not being interested because they haven't established their working personas yet. I notice that people will make a character with a preliminary idea, but then they often change the concept slightly (or dramatically) once the character hits the world. To allow for this I have to be able to see the character in his actual habitat before I try and hook for a big story.
I also do not make flow charts or even set end results most of the time. I proceed now from the idea that my story is the least important thing, and that the players will communicate what they are interested in if I but listen and observe.
Oh and another thing. Good NPCs are essential. By this I don't mean full stat blocks and all that, I mean details that make them memorable and creating ties between NPCs. I constantly try to connect NPCs in ways that make sense or are entertaining. When you re-use memorable NPCs and connect them where possible/reasonable it produces something that the players can use for a sense of structure or consistency.
