I think you should be willing to give up any EXTRA space you are taking up. The seat your purse is in is extra. The two seats your fanny is in isn't.
Efficiency is not the only thing to strive for on a bus. There's also fairness and accommodation of bodily issues and the concept of first-come, first-served, and there isn't necessarily a one-size-fits-all answer to every question either.
To illustrate that no one truly believes the most important thing is to use the space efficiently, on our city buses, when someone gets on in a wheelchair, two seats are folded up in order to safely anchor the chair. Surely no one would suggest that the person in a wheelchair should then have to get off if someone gets on who could theoretically sit in those two seats--that would be reprehensible.
Needing extra space is a little different as I don't think it's covered by law, but I do think it would be rather dehumanizing to class people above a certain size as "people who must always get up to let others sit."
On a conveyance that is sold by-the-seat, like a Greyhound bus, then there's really no way around the fact that someone may need to sit in the other seat even if it's cramped. I, no small person myself, ended up sitting next to someone who took up a large portion of my seat for a Greyhound ride once. It was uncomfortable, but we did all get where we were going.
But on something like a city bus, where you're paying to be on the bus
and there's no guarantee of a seat, I do think it's special needs first (such as elderly/pregnant/mobility issues) and then first come first served, even if it means the space usage is not perfectly efficient. It's not a math problem about fitting boxes into the bus, it's people, and thus etiquette applies. And I think things like accommodating special needs and honoring first come first served are parts of etiquette.