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It's good practice to try out methods for yourself on dummy pages until you find something that works for you, before you dive into your project for real.
I inherited one site that had over 50 separate elements on a page, all positioned absolutely relative to the BODY element. What a labor that page builder must have gone through finding all those x,y cordinates! But the page was almost all images and it made a kind of sense to put the slices together that way.
A more liquid layout -- one that uses padding, margins, etc -- has proved the most practical for me so far. Absolute positioning on a grand scale tends to buld up the size of the code. You need either a separate ID for each element or you need inline style attributes for each element, and it can create a maintenance hell.
Plus, if there is text involved, a user stylesheet override could cause a major mess.
Personally I lean toward a mixture of the two. I like to absolutely position elements like left/right navigation and then give the content area margin/padding to compensate for the space taken by the nav element.
This creates a semi-fluid design with one or two elements fixed and the rest liquid.