I know this is delayed, but considering I am working on a similar project, I thought I would chime in.
Why exactly are you thinking that implementing a framework via Page Layouts is a better approach than via a Master Page? My approach would be to have a single custom Master Page that dictates the structure for the core container of the design, including your normal header content (such as logo and top navigation). From here, you would register your custom CSS file that is registered after COREv4 that would dictate the styles used within your framework.
The publishing page layouts would then have the core content area's markup that includes your necessary semantic HTML5 markup that is referenced within your style sheet. This would allow you to have a single custom master page with your custom css file and then spin up multiple (varying) page layouts with all the necessary mark up to display your content.
From these page layouts, you would be able override the default content placeholders with page-specific markup and CSS if necessary (i.e. -replace the logo or top navigation on a single page layout or apply a specific style to a page element when a specific page layout is used).
The real key (in my opinion) is ensuring your custom CSS is registered after corev4 and that you pay attention to CSS specificity to make sure that your styles aren't being overridden by corev4.