This is how I understand it: Mesa recommends using the 100w setting AND the 4ohm output with a quartet of 6V6s because the output impedance matches better that way. This is for the same reason that they print on the back of the chassis, near the speaker jacks above the 4ohm output: "Use with 50w setting". When you cut the power output in half, you ideally want to mismatch your output to speaker impedance by 2x (4ohm output to 8ohm load) to compensate. Mesa doesn't make a big deal out of it because the amps are tough enough to deal with most mismatches, and having potentially two different power settings at the same time (e.g., 50w Ch1 and 100w Ch2) just confuses things. Ultimately, it doesn't matter that much under most circumstances. (BUT PLEASE look at the manual for safe and UNsafe impedance mismatches!!!)
I think that would also mean using the 50w setting with 6V6s -- in other words, using just a pair of 6V6s and actually producing more like 25 watts -- would imply an ideal match another level up, like using a 16ohm load on the 4ohm output. (Do NOT quote me on this.) But again, Mesas are tough, and using the 50 watt setting with 6V6s and an 8ohm load on the 4ohm output is just fine. In fact, I've been doing this for months now and I couldn't be happier.
Most modern 6V6s can handle the full-power setting fine too, by the way. Tweed will help them last longer though, which is also true for 6L6s and the rest.