My reciever only allows one crossover setting (which I have set at 80 hz). However, I think the M22's can go down to 60hz. If I set the fronts (the M22's) to large and the sub to "plus", will the M22's suffer any from the low frequencies?

Mario, welcome back. The commonly suggested 80Hz crossover setting is what I use on my M22s although I have available 40Hz-200Hz. 80Hz has been found by THX and others to be a good compromise setting, being high enough to relieve the speakers(and the amplifier driving them)from a significant part of the lowest bass burden while not being so high that the sub is easily localizable. No, don't set the M22s large and don't use a "plus" type of setting. Use bass management to allow the sub and speakers to handle the frequencies which they're best at.

I'll probably just keep it at 80hz. I was just bored and messing around with my reciever settings (I just recently rediscovered the manual). I recently got my QS4's and EP350 to complete my M22's and VP150, so I've just been listening to movies and music nonstop and tweaking the settings.

I ran my M22s as large LFE+ for quite sometime and enjoyed it. The M22 driver just does a natural roll off of any frequencies it can't handle, so no you won't hurt them. I would suggest running your system the way it sounds best to you. If you like the M22s set to large then run them that way.