Assuming both speakers are the same impedance, and close to the same power handling, there shouldn't be a problem. If one speaker has a sensitivity of about 3 dB more than the other, that one will perceived as louder. That can be a plus in a vertical cab. Put the louder speaker in the bottom, so it will match the softer speaker that's closer to your ears.
If each speaker has a different impedance, the one with lower resistance will absorb more power and be louder.
How are the speaker jacks labeled? Typically, Mesa amps have one 8 ohm speaker out and two 4 ohm outs.
Now, here's where it gets tricky: contrary to common sense, the two 4 ohm jacks are NOT meant for one 4 ohm speaker from each jack.
They are designed to handle ONE EIGHT OHM speaker (or cab) from EACH jack.
The same holds true for a Mesa amp with two 16 ohm jacks. They want to see an 8 ohm load at each jack.
You don't have to believe me, just look in any Mesa owner's manual. All of them are available at the Mesa website.
Two 8 ohm speakers in parallel will have a total impedance of 4 ohms.
In series, you get 16 ohms. Them's your choices. You can't get 8 ohms from two 8 ohm speakers.
However, you are allowed to experiment to a certain degree. The manuals even encourage it. Try plugging the 4 ohm cab into the 4 ohm jack, then compare it to the 8 ohm jack, etc. You may prefer the sound and feel. It's safest to put the amp on standby before unplugging speakers. Tube amps don't like being run without a speaker plugged in.
Mesa amps can handle a 100% mis-match, up or down. Mesa (and Fender), not Marshall.
As far as two speakers with different power ratings:
The rule of thumb is to take the lowest rated speaker's power rating and multiply that by the number of speakers. In the case of a 25 watt speaker paired with a 200 watt speaker, 25 x 2 = 50 watts is a maximum safe power handling for the pair.
In your case of a 50 watt paired with a 60 watt, the safe power level would be 100 watts. Not 110, but, yeah, it's only 10 watts.
