I'll start by pointing out that it's less expensive (and more flexible) to build two stand alone 12/6s, each with Alpha mid drivers, than a 12/6 with 18Sound mid driver and a 12/sub.
I've been using one or two 12/6s for almost four years in a variety of situations, but always with amps capable of around 400 watts @ 8 and 750 watts @ 4. (Not really that much more than the LittleMark II.) Keeping in mind that I'm a grumpy old man who doesn't like stage volume high enough to require ear protection, here are some of my experiences:
Outdoors, on a fairly large open-backed stage, a single 12/6 can do OK as a personal monitor, but there needs to be good monitoring for the rest of the band. In more compact outdoor settings, and with a wall behind the band, a single 12/6 can cover the stage as long as the overall stage volume is reasonable.
In typical bars, with a rock band working at reasonable levels, a single 12/6 can carry the room. In tight spaces, standing directly in front of the cabinet, it can get loud enough that I have trouble hearing the drums.
In moderate sized rooms, or if I'm going into an unkown situation, I always bring both cabinets. But if the sound system is adequate, I'll sometimes only plug the top one in.
I've had no complaints when I've supplied my 2 x 12/6 rig as backline for multi-performer benefit shows that included loud metal-type bands and no PA support for the bass guitars.
I've subbed in a really loud band where the snare was the only part of the kit I could hear unless I stood tight to it. My pair of 12/6s and GK-1001RB-II carried the room, verified by two of my sons who stopped in to hear the band.