In my humble opinion, you should route all your guitars to a guitar bus, vocals to a vocal bus, harmonies to a harmony bus, keys to a key bus, drums to a drum bus, etc.
You should then route ALL of those buses to a Master Bus which dumps audio to your audio card (i.e., when you mute the Master bus, there is NO sound).
Why? A whole slew of reasons.
Number One is that you can turn off (mute) whole groups of instruments/vocals/harmonies, so that you can properly mix/fix other stuff.
Number two is that you can put plugins on, for example, all the vocal tracks, by putting the effect on the Vocal Bus.
Number Three is that you can use the Master Bus to [attempt to] master your whole mix with compression, EQ, etc.