I would suggest one zone per room, ie. air/floor stat in room + actuator at manifold and suitable controller. Depending on number of rooms you may need more than one manifold/controller - I have 2 manifolds in 2200 sq.ft bungalow, one with 8 zones + towel rad, other with 6 zones + towel rad.
I have seen some suggestions that only one or two stats for whole house would be sufficient but I don't like the idea of such limited control - but maybe that's just me.