splatcollision's answer is double-triple good, so I won't try to revisit any of what he said, except to say that having done it once (fairly painfully, though that was before Sass and Less were as pervasive), I've found 'Skeleton'[1] to be a great head start (if you're willing to use its grid system, which I like a ton more than any other grid system I've seen.)

[1] - http://getskeleton.com/