I like the concept of keeping the Flirc simple and true to an IR-USB input device, without requiring additional software beyond initial setup. In fact I LOVE that aspect of it.
However there are certainly applications for having multiple profiles. For example, I mostly use Plex on my HTPC, which I have mapped through Flirc to be controlled with my TV remote. Occasionally I'll use Media Center for Netflix duties however, and this uses a completely different set of keyboard shortcuts than Plex. For example, the pause button on Plex is space bar, but for Media Center it's Ctrl+P. Thus I cannot use the same remote for both apps without profile switching.
The workaround as far as I can tell is to use another remote, or setup another profile on a Harmony remote, and program the additional Media Center buttons to this remote/profile. Of course during playback you have to remember to use the right remote/profile for the particular app you're in; a task a computer is better suited to handle in the first place IMO.
If you're looking for an example in the human interface device space, Logitech supports automatic profile switching for their G-series mice and keyboards. They store these profiles on the mouse/keyboard itself, and utilize pre-installed Logitech software to tell the device which profile to use at any particular time. Definitely a bit more complex, but extremely powerful at the same time.