etymology time
it just came to me today that the title is an Italian word. I was reading a book and the word was in there and i'd just finished watching.

I dug a little deeper (while seeing which VAs are which characters) and found that Narita, the creator, translates the title to "Stupid commotion!" (literally it is: "uproar/din", but 'commotion' is spot on as well.) 'Ruckus' would also be a good one.

The most common spoken expression seems to fit the creator's definition, as it's usually a derisive term: Che cos'e tutto questo baccano!?' - What is all of this
ruckus about!?

You can also fare baccano - (literally 'to do uproar') but is often understood as 'To start/create an uproar'

and, for the main character thing, I'm tempted to go with the 'no main character' thing... but the OP seems to focus so much on the duo of Isaac and Maria that, well, it just almost has to be them...