Blue Flavor has an interesting blog post on designing with out a grid. Very good read, and while I tend to stick pretty strict to grids, sometimes they can confine your thought and design process. There have been a few instances where I designed with out a grid, and afterwards cleaned up the margins by developing a grid.
If you are interested in grid, or grid-less design check out Making and Breaking the Grid. Great book with tons of excellent grid and grid-less examples.