Rule of Thumb: When using multiple speakers, choose speakers which match (like in a 4x10), align them (also like in a 4x10), and put them close together (like they do in 4x10s). This will minimize phase artifacts, yielding the purest sound and most efficient use of energy (=loudest). Mixing drivers can result in drivers pushing in opposing directions because different drivers will respond slightly differently to the signal.
That said, many people mix speakers for taste or because they hope the speakers compliment each other well.
This is sort of like pickups on a Jazz Bass. Using one pickup will give you a purer sound which is more evenly balanced. Mixing the two pickups will introduce phase cancellation, which can be used for good effect. Although some people do it, many people would dislike using both pickups equally all the time because it is like an effect which cannot be turned off.
Guitarists mix speakers more often. Since their wavelengths are (generally) shorter, it is less likely to offend.