Problem solved: Take a taxi (or an arranged car) to the San Basilio cruise terminal (not to be confused with the HUGE cruise terminal). From there, it would be (I'm guessing) a 20-ish minute walk to the San Marcos area. Many may post that cars of any type are not allowed on the main Island of Venice, but I can assure you we took an arranged car from the San Basilio cruise terminal to the airport when we disembarked at the end of the cruise. It's about a 20-minute ride, give or take 5/10 minutes depending on time of day/traffic. But, to clarify, personal vehicles/rental cars, etc, are NOT allowed, just taxis and arranged car services (with approved drivers).
When we were in Venice, we took the vaporetto from the San Marcos area to San Basilio to catch our small-ship cruise (SeaCloud), but we had also considered just walking it. We travel carry-on only, using the RS rollaboard. But, you likely know many of the bridges include several stairs, so that means you will need to carry your luggage up/down several times.
But, take a look on a map to determine if you think the walk would be do-able for the two of you. I would not want to do in a rain storm, but otherwise, it would work okay for me, if I could not (medically) go on a boat.
But, HUGE DISCLAIMER, what I don't know is if someone has to have any sort of advance reservations arranged thru the San Basilio terminal in order to have a vehicle have access, since the vehicle that met us when we departed at the end of the cruise was arranged through our ship. Your hotel might be able to advise. And, your hotel may also be able to advise what arrangements can be made for someone who just can't medically travel by boat. If you are staying at a very small hotel that does not have such information, you could always just telephone one of the larger, high-end hotels and talk with a concierge (and just not explain where you plan to stay).