I have just about finished converting my site design to the Genesis Theme Framework by StudioPress. It really is the first, what I would consider to be a framework, that I have used. I have used what others may call frameworks in the past but pretty much all of them lacked the most powerful aspect of the modern frameworks, hooks. A hook is a function that allows the designer to insert HTML and in the case of Genesis, PHP, into the design outside of the normal flow of the design. For example Genesis provides hooks for inserting before and after the title, content, loop, etc. StudioPress even provides a plugin that makes it dead simple to insert your code using the hooks. You can even disable a standard Genesis function and use your own code.
The current design is using hooks to insert the date before the title, the edit link after the title, and the post footer after the post content. It also uses it to do the footer by disabling the standard Genesis footer in favor of my own. All in all it took me about 8-10 hours to get the site looking like it does now. The majority of that time was spent looking at the site through Developer Tools to target the exact elements to style them. Getting the specificity right for the CSS can be challenging, but not terrible. However, that time is considerably less than what it took to get the old theme written. I have to acknowledge though that I have gotten more proficient with CSS, PHP , and HTML and that I was able to copy some code from the old theme. I would still argue that you would see much faster times to completion on designs than if you are not using a framework at all.
There are still a few things to tweak like getting the edit post link to be on the same line as the title, preventing the post footer from displaying on pages and getting my Typekit fonts working again. I don’t see those taking very long and if I encounter any difficulties the support forums at StudioPress totally rocked it for me. There are other frameworks out there like Carrington and Hybrid (a couple that I have tried) and themes that allow for tons of modification through options (like WooThemes Canvas theme), but I would highly recommend Genesis and the Simple Hooks plugin if you are considering putting your design on top of a framework.