Multiple placeholders are to provide support for being able to provide content for different areas of your master layout. Typically you would have, at a minimum, a main content area. But you might also want to have an area in a left nav column that you could add something to on a page by page basis. Or perhaps there is a content placeholder in the <head> tag (which the master page template creates). This would allow you to create scripts or other page elements that should live in the page head and they will be included in the appropriate place when the content page and master layout are merged.
You can position the content placeholders by whatever means you see fit. You could use traditional tabular layout or use fixed position divs around the content placeholders. That's just a question of how you prefer to do that with regular HTML.
-Peter
compiledthoughts.com