Onhwy61 made very good points. Kind of what I was getting at in the end of my post, but better stated and more thorough. I agree, it will depend largely upon the room, construction, contents, treatments, system location, room openings, etc. Unlike him, though, I have not heard larger speakers sound up to their potential in a smaller room, and have much more frequently heard problems with that kind of arrangement. That's not to say he's wrong and that it cannot be done, it simply has not been my experience. More often than not I've found it visually and acoustically overwhelming with a distortion of scale, in relation to the room, that tends to inhibit my suspension of disbelief. I've also experienced these kind of setups can often limit soundstaging potential. Notable exception have been asymmetrical corner arrangements. Again, this is in my limited experience and YMMV.
I use a sub as well, but tend to turn it off more for music as I think, in my case the single sub is slightly detrimental to imaging, and my speakers already go down pretty low. Two or more would be better, IMO.