create layouts without the use of embedded regions from my experience with Drupal, I could understand, that you can thematize the page.tpl.php file, adding the appropriate html / css and entering regions with php.
So far so good ....
but my approach I'm following this project is to thematize the file. tpl.php corresponding to each of my content type. Now I need a page to bring them all together, I did it successfully using the "Panel". But I would adopt the approach in my opinion the most flexible layout with html / css.
On which page should gather instances of my various themed content type?
Your best option really is Panels, especially once you get comfortable making your own panel layouts (which is actually quite easy).  Along with using preprocess hooks to attach classes (particularly to body) as needed, the combination of the three lets you do pretty much anything you want.  I have yet to been given a design treatment from my creative director (and they are all complex) that I have not been able to tackle this way.