Wireless thermostats allow you to put it where y0u want, when you want, or even take it with you when you go up or downstairs.
Sealing off ducts does not save energy- it creates pressure imbalances that only increase the amount of air handler driven infiltration. (This effect has been measured both in laboratory setting and in-situ in existing houses by researchers at the Lawrence Berkeley National Labs.) Better balance can also be achieved by increasing the duct or register capacity on the "cold" part rather than taping off supply ducts in the "hot" part of the house. Ducts need to be balanced too- the lack of dedicated returns on the lower floor are part of the problem.
In earlier posts you mention "...a full first floor gut in the plans...", then later on "...until I can gut basement." Is this a 2-story + basement, a walkout basement with a floor above or something else? The heat loss characteristics of basements are fairly different from fully above-grade floors, which makes running as a single zone nearly impossible to temperature balance, since the balance changes with the weather.
A pair of mini-splits can work, provided the floor plans on each floor are sufficiently open. It becomes an issue for doored off rooms down the hall from the room with the wall coil. Sometimes mini-duct cassettes feeding a few adjacent rooms is more effective. More so than single speed hot air furnaces, sizing a modulating mini-split correctly to the load is important for both comfort & efficiency.