What may help is thinking 'backwards'. E.g. you know the main character's goal, and you start imagining what obstacles could be put in between him and his goal. For instance, if you look at Monkey Island 2, the goal is finding the four map pieces - and the first obstacles that come to mind are the fact the the current owners don't want to relinguish them. Go from there.
And remember to find multiple uses for items, npcs and locations!
And remember to find multiple uses for items, npcs and locations!