Thermostat location in 3 story building

A dual-zone system is one heating element and/or AC coil serving two separate ductwork segments. The extra cost of a dual-zone system as opposed to a single-zone system is in the dual-zone temperature monitoring/control panels, and a system-controlled diverter that sends the air to the side of the system that needs it (or both).

The upsides:

• One interior and one exterior unit to buy/maintain. Drastically reduces most routine maintenance costs and generally increases MTBF.
• Easier to balance your home's ventilation; you don't have to worry about the relative heating/cooling capacity of two units versus the space they're expected to cover.
• Dual-zone systems usually have a "master/slave" control panel arrangement allowing the "master" panel to control both zones while the "slave" panel can either also control both or only control the secondary zone, possibly with additional restrictions like max/min temperature that can be set on the master panel.

The downsides:

• No backup; if something on the one unit goes, there is no heated/cooled air anywhere in your home.
• Impossible to differentiate the electric costs of you versus an upstairs tenant.
• Longer ventilation runs to the second zone, depending on home design; the second zone needs vents and returns run from the main unit to a usually distant part of the home. These longer runs will not be as efficient.
• To supply ample heated/cooled air to both zones at once, the unit must usually be a bit beefier than a comparable single-zone system, to compensate for inefficiencies and maintain desired airflow when both zones are being ventilated.
• You cannot have the heat on in one zone and the A/C on in another. The entire system must be set to heat or cooling, meaning if your tenant likes it substantially warmer or cooler than you do, the ability of the system to provide the proper temperatures can be limited at times.

A dual-unit system will have two separate single-zone HVAC units each controlling one area of the home (upstairs-downstairs is common in new construction, as is having a second HVAC for a new addition).

The upsides:

• Having a backup system means at least some of your house can still be heated or cooled in the event of a failure of one unit.
• Vent runs can usually be shorter, as the units can be strategically placed in new construction for the most efficient ductwork layout to each zone.
• Each unit can be smaller than a single unit for the whole house would have to be, meaning the exterior units can be located in tight spaces or more easily hidden behind shrubs.
• By hooking the second HVAC along with all upstairs circuits to a sub-meter, you can easily determine (and sever) the electrical costs of an income property.

The downsides:

• More expensive to put in than a single unit, even a dual-zone. Two 1-ton units will cost more than a 2-ton.
• Maintenance costs also increase; with two units the MTBF of a single unit in the home is halved, meaning on average you'll have to call the repair guy twice as often.
• Less centralized control. There are some nice thermostats that can communicate wirelessly (usually as part of a whole-house automation/alarm system), but basically each unit will be its own completely separate system and to balance the temperature in the whole house you must go upstairs and down to fiddle with settings.

I think you are saying that you have two zones on one boiler, each fed by its own pump and thermostat (i.e. the radiators have been converted to hot water). My answer is based on this assumption.

Since they're both on the same boiler, the water is heated with equal fuel efficiency.

The two loops probably are different in how efficiently they transfer that heat to the room. Low efficiency in transferring heat to the room will decrease the heating capacity of your boiler, which is a problem if you can't get the house warm enough on a cold night. But as long as you're keeping up with heat demand, efficiency in transferring heat doesn't make a difference with fuel usage. (You can tell how efficient they are in transferring heat to the room by feeling the temperature at the end of the loop -- if it's pretty cold, the heat was transferred to the room very well)

So, the answer is that you should set the thermostats to the lowest temperature where you're comfortable. Your addition from 2000 likely has a lot more insulation than the original 1939 house (in 2000 the building code required a lot of insulation, 1939 not so much), so if you want to pick the more efficient one to heat, heat the addition not the main house. It will be more efficient because you'll lose less heat because of the greater insulation.