Swapping out my B&W 601S2s for a set of Thiel CS2.4SEs, the biggest difference was in movie soundtracks. Movie scores can be epic.. grand, large in scale and generally benefit from a good stereo speaker.
In terms of frequency responses, a good AV receiver's bass management should be able to send the low frequencies from the mains to the sub, if you set the speakers to small, so theoretically, you aren't losing anything.
But it makes the main speakers sound, well, small :)
Putting them to full range IMHO gives movies with orchestral pieces the scale and grandeur they deserve.