Trent Walton has an excellent post on getting started with Responsive Web Design. He writes…
Whether it’s CSS for a single component or an entire site, I finish in a mobile-first fashion by using min-width media queries to set the smallest view and move outward from there. However, I start much differently. I begin with wide views because the layout is usually more complex. I find it easier to ensure columns and spacing are set wide and work my way down to a single column.
I know it goes against the letter of mobile first to design the big screen layout first, but I do that, too, and for pretty much the same reasons Trent describes.
Trent’s article is awesome, by the way. Go read the whole thing now.