Flow layout emits the type of HTML you are most familiar with, which (if
designed properly) can scale to the user's resolution.
Grid layout is designed to be very VB-ish in the designer. You put things
where you want them, and they will be exactly there. It achieves this using
absolute positioning of each HTML element on the page, which is measured in
pixels. Everything is always in exactly the same place, whether you are
looking at it on an 800 x 600 display or a 1920 x 1200 display.
My preference (in case it wasn't obvious) is for flow layout - I think it's
irresponsible of designers to target the lowest common denominator with a
specific number of pixels. Take a look at cnn.com or msn.com on a high-dpi
widescreen monitor, and you'll get a feel for just how much this kind of
rigid design sucks when in an environment for which it wasn't optimized. The
web is objectively different than print, and it's irresponsible that layouts
(particularly of huge sites like these) don't leverage the platform.
Not that I have strong feelings about this or anything...
That being said, it is a lot easier to get things exactly where you want,
and do so really fast, using the grid layout, so it's not always
inappropriate.