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If I understand the topic, the initial problem in front of us is to determine what goes on the page (the big blocks), not necessarily where it goes on the page, right?
For a general web site, the primary components are
* Header
* Navigation
* Content
* Footer
Pretty basic. Now break the big sections into the XOOPS blocks (left, center-left, center-right, center-center, content, right, banner). There's your (x)html.
CSSZengarden does the same - here's the html (no positioning is done there), add your css and graphics to make it look the way you want.
Then add your other criteria - scalable, fluid, cross-browser compatible, CSS1/2 valid, accessible, language friendly (UTF-8 discussions elsewhere).
That's how I would start...