Bigger boats tend to have a slower, easier motion, which means they are less tiring to sail, and you collect fewer banged shins.
I know this from personal experience: Eric Forsyth's 42-foot Fiona has a much easier motion that my 23-foot Blue Moon, though they are both heavy displacement full keel boats. Being a passenger on Fiona is much less tiring than being a passenger on the Blue Moon.
Being a crew member, on the other hand, is a different story. Particularly when the wind begins to blow, and the waves begin to roll.
It's much easier/safer to move about on Fiona's deck, for example, simply because she's not being tossed about quite so much as the Blue Moon would in the same sea conditions.
But it is much more difficult to wrestle with Fiona's massive sails, compared to the Blue Moon's smaller ones. Tradition says a man can handle up to a 400 square foot sail. Fiona's main is 440 square feet, while the Blue Moon's is 170 square feet.
In a fresh breeze, that can mean the difference between 340 vs. 880 lbs of pressure on the sail. I can easily manage the Blue Moon's mainsail with a two-part purchase on the halyard, a three-part purchase on the sheet, and a bit of muscle power. Fiona on the other hand requires a heavy duty winch on the halyard, a multi-part purchase on the sheet, and she still tested my limits of strength and endurance when it came time to reef her in a blow.
And while the Blue Moon's mainsail can be worked at deck level, reefing Fiona requires climbing on top of a tall cabin top (from a deck that is already much higher above sea level), and often standing on tip-toe to pull down a stuck slide. That difference in height means a lot when the boat is trying to pitch you into the sea. More scary/fatiguing, not less.
And that's not even mentioning Fiona's massive, polled-out genoa, which I called the Monster. Any adjustment of that sail meant many minutes of nearly impossible work on a pitching, rolling deck.
All in all, I would say it is much more tiring to be a member of Fiona's crew, than the Blue Moon's.
So where is the balance point? Where does the fatigue caused by the more tiring motion of a small boat balance with the more exhausting labor required by a big boat?
And how do other factors affect the balance?
For example, a ketch typically has smaller sails, which make it easier to handle them individually, but there are more of them. Where do they balance?
A flush deck makes it possible to work the sails at deck level, but would that advantage be counter-balanced by reduced ventilation? Does ventilation really matter at sea? Eric would never let us open the ports or hatches anyway!
So if Fiona is too big (and she is, at least for me) and the Blue Moon is too small, then where is the balance?
It's a paradox...
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