In Responsive HTML5, the topic content is displayed inside an iframe. In Frameless, there is no iframe. I think you just pick the one you like the look of most, unless your organisation has some specific technical requirement not to use iframes. From a purely non-technical user perspective, I don't see much difference besides aesthetics.
I think both outputs are supposed to be 508 compliant, which I think it a US government accessibility requirement. I can't comment first-hand on the accessibility though.