Are heavy-duty 40-sheet punches actually easier to use than 12-sheet ones?

Counterintuitively, yes for thick stacks. Reviewers on Amazon and Walmart consistently say the longer-lever, 'reduced effort' designs like the Bostitch EZ Squeeze and the AFMAT HPX series take noticeably less hand strength than smaller punches once you go past about 6–8 sheets. For a single sheet, though, a small 12-sheet punch is faster and lighter on the desk.