I can talk aesthetics only, because I built my first 5.1 system just a few months ago. Logically I know that using a bookshelf speaker for a center should be fine. And if the tweeter's dispersal pattern is wide enough top to bottom, the same speaker should work laid on its side. But to my eyes, it would just look wrong. I like having a low, horizontal center that almost spans the TV's width.
Gmichael mentioned loving his bookshelf center in his bedroom set-up. Good!
And for that application, I could live with it just fine. But for my main set-up--the one friends will see and hear--I'd much prefer a low, horizontal center. Just my humble opinion.
Or I can see using three towers, assuming the center tower isn't too big to fit comfortably above or below the TV while on its side. But then again there'd be the question of the tweeter's dispersal pattern. Would guests sitting off to the side of the room get the full effect of the center's tweeter?
Chris
P.S. One more thought: Unless you laid the bookshelf speaker on its side, it'd be harder to fit it into a typical HT set-up, right?