Preface: Not a professional web artist.
I've found that there's way too many fiddly bits to get things to flow just so at cell-phone and uber-widescreen sizes, especially in anything of reasonably interesting complexity.
Typically, I design around having a fixed-width site in some fashion; usually bounded at [600,1200].
I also find super-wide columns of content to be a hassle to read. I seem to remember that there's some research which suggests an optimal number of words per column line.
