I think it works fine (being that I’m running such a game), but the CRB and GMG don’t provide much guidance for doing so. The assumption is you’re playing a story-driven game, and things like sandboxes and hexcrawls are another way to experience that (or to “decide how to go about it” as the sidebar on p. 44 of the GMG suggests). However, the tools are there if you know how to use them.