How to balance thermostat settings between zones to maximize efficiency?
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.