Power handling. One speaker that can cope with the entire output of a 100 Watt amp is probably not very efficient, so you would waste a lot of the power. A 4x12" with speakers rated at 30 Watts each would produce a higher SPL for the same power.

There's also sound spread to consider. A single speaker in an open-back cab will distribute sound quite evenly. Multi-speaker cabs tend to focus the sound into a 'beam' from the front of the cab. Closed-back cabs increase this effect, because there is no sound from the rear of the cab.