One of the big factors is the room and your listening position. My setup is in my living room which opens to the dining room and kitchen. When I'm in the kitchen and playing music at times I like to use 5 channel modes, either a multi channel stereo or matrixed mode because the sound envelops more area this way (without necessarily sounding better). However when sitting in my living room in the prime listening position 2-channel Stereo is superior and sounds most musical.
Also many people will argue about the usefulness of a center channel, the one thing I would say is if you're going to use it don't go cheap on it or you'll regret it when watching movies. When I first upgraded to a 5.1 I assumed it wasn't that important so I bought a cheap entry level center, after watching two movies and listening to the centre struggle to keep up with the rest of the system I brought it back to the store. Now that I have a good quality center movies are a pleasure regardless of where you're sitting in the room.
