Using HTML elements to produce the boxes for a region chain is a point of contention. The point made against the current version of the spec is that combining content and presentational code should be avoided when possible. At TPAC 2012, Bert mentioned that using an external file to define the presentational boxes would be OK.
One way to use an external file for presentational purposes is being defined by the Web Components effort, so it may be a useful experiment to see how we could define regions using custom elements and/or decorators from Web Components
Let's take a very simple example of regions use, so that the different versions are more easily compared. This simple example just has two regions, the first being 60% of the height of the viewport. The named flow is then interrupted by an image, and resumes afterwards in a second region. You can take this basic structure and scale it up to a more complex layout such as the one found in Appendix A where the regions again flow around an image, but are positioned inside and outside a grid element.
Here's the starting point with empty presentational elements in the content markup:
Using custom elements, you could put the presentational elements in a separate HTML file. I have extended the img element here, but you could instead extend the body element.
Or you could use decorators. Again, I chose to add a class to the img element, but you could decorate the body element if that's your preference.