Thanks for your replies. All good info and suggestions. While I understand a lot of this is personal preference, I wanted feedback fromt the forum to make an informed decision.
The main problem I see with that Mother Lode is that it weighs 8.7 pounds empty! There are similar bags available these days that weigh about half that much. I've used all the types of public transportation you list for trips of similar length, traveling by myself. I limit my fully packed 2-wheeled roller bags to 20 pounds. So the lighter the empty bag, the better for me.
I've been considing new wheeled bags for this very reason, @Lo. I just haven't been able to justify it up to this point because the MotherLode bags are in near-perfect condition even after all these years. The 4-ish pound wheeled bags you mention: do you have a fav?
I'm sure you're aware of the stairs and ramps you'll encounter in the public transportation places where you'll depart and arrive, as well as of the often crowded high rise and narrow tread steps into and out of trains and buses. With boats (vaporetti included), you get the added fun of a moving floor when getting on and off. All these situations are awkward whether you use your current 47.5L roller bag or your 41L backpack
Yes, that has been part of our consideration. The last time I was in Venice it was part of an 8-day Italy trip with a rental car, so we basically just packed a bit-larger backpack for the trip and transfers were not an issue.
What's more important is how much stuff you take. The more you take, the heavier the bag and that becomes a hassle whether it's being wheeled or carried on your back. If you're not used to backpacks, my suggestion, since you already have them, is load your backpack with the same approximate weight you take with you and go out for a walk. Make sure to hit some stairs. Then decide if this will work for you. It doesn't matter if it works for someone else. Will it work for you?
I completely agree about the "more stuff you pack, the heavier the bag." Our friends are constantly amazed that we can travel to places like Patagonia, China, New Zealand, Europe, etc with just a carry-on and a day pack. Less is best! I have not walked a distance with 20+ pounds on my back for a while, so I've been thinking of doing several "loaded" walks on the flat and stairs as you suggested. That well could be the deciding factor.