It's not a dumb question, and most amp companies (including Mesa) do a poor job of labeling their amps - it's confusing because the rules for multiple speakers or cabs are different from one. Modern Laneys show the way to do it - around each jack or pair of jacks there is a printed box telling you exactly what combination of cab impedances to plug in there.
In fact, on the Mesa amps, the jacks that are labeled 4 ohms are not 4 ohms *each*, they're 4 ohms *for the pair*... big difference. (Same with the amps that have two 8-ohm jacks.)
Next, when you connect two cabs, either directly to the amp or by daisy-chaining, the total impedance is half that of either cab - so if you're using two 8-ohm cabs, that's a 4-ohm load in total... so you use the 4-ohm jacks (one or both). Almost all amps and cabs are wired so that pairs of jacks are in parallel, even when daisy-chaining - series wiring is different and I won't confuse you just yet!
But - only daisy-chain if your amp doesn't have two of the right impedance jacks (eg if you have two 16-ohm cabs and an amp with only one 8-ohm jack), or if you don't have a cable long enough to reach the lower cab - because, if the first cable from the amp to the top cab fails or comes out, the amp has no load and you'll quite likely blow something (tubes or output transformer)... whereas if you run two separate cables from the amp to the cabs, it would need a problem with *both* cables to do that.
You can run cabs of different sizes if they're the same impedance - only the impedance and power handling matters... for cabs of the same impedance, half the amp's power goes to each cab, you don't just add them up. (eg a 50W cab and a 300W cab is a 100W pair, not a 350W pair, because half the power goes to the 50W cab and if you go over 100W input to both, you'll blow it.)
You can even run cabs of different impedance if you know what you're doing - the easiest rule to remember is that you treat the pair as if both are the *lower* of the two impedances (eg an 8 ohm and a 16 ohm together should still be run at 4 ohms on the amp, as if both were 8 ohms) and that the majority of the power goes to the lower impedance too (2/3 to the lower, if one cab is half the impedance of the other).