It's easier and more efficient when your mouse doesn't have a third button. Isn't that what we're talking about? Mice that don't have the ideal third button (or one at all)?

Trying to press down a scroll wheel as a third button seems to always be an exercise in frustration as has been mentioned. As I'm still moving the mouse cursor around, I'm already moving my left hand to the key, so that by the time I click, it's all a single action.

I'm also fond of using the key modifier method when using a trackpad that doesn't have three dedicated buttons. It's easier/faster than having a special gesture or region because I can move both hands, each to an easy target, faster than one hand to a specific point on the pad.