The best approach for a new central heating and cooling system – in what concerns its ductwork – is a short and as straight as possible system, located in the conditioned space of the building.
If possible, do not install the ducts in your garage, basement or attic.
Even well sealed and well insulated ducts will leak and lose heat (or cool air, in the summer). That’s inevitable, and many experts are now recommending the installation of ducts within the conditioned space of the house; if the loss happens in the living space, duct leakage becomes less critical.
We "just" have to hide the ducts in corners of rooms, or in dropped ceilings, or consider an insulated chase built into raised floors or extending into the attic.
Location and design
Also consider round-rigid metal ducts and a central location for your heating and cooling system.
Discuss with your design builder the best way of implementing a short system. Avoid as much as possible long runs, 90º pieces and square corners for your ducts. Consider Y-joints instead of T's for the corners. In a two-story home consider a system sending branch lines for the second floor rooms up through a center wall, to minimize the size of the ducts.
A small duct system
That’s rather obvious: a poorly designed duct system, without properly sized heating/cooling equipment will waste energy, no matter how well sealed or how well insulated the ducts are, or how efficient the equipment is.
Even a duct system without leaks and conveniently insulated may cause problems. It’s difficult to distribute air properly throughout a large house, keeping all rooms at consistent temperatures. Rooms with too large or inefficient windows, or leaky or with poor insulation, or rooms in sunny or windy parts of the house, may have very different heating and cooling needs...
One way of overcoming this problem, in new construction, is to build very high insulated homes, with very high levels of sealing and high-performance windows - homes that will need small heating and cooling systems, with very short duct systems.
That’s easy to implement in moderate climates, and not impossible to achieve in cold climates - as long as your home is properly sized (it can’t be too large), shaped (a compact shape will be advantageous), properly oriented to the sun, protected from the cold winds and massively insulated and sealed all over their envelope.
Duct systems and zoning
Common duct designs for large homes with conventional levels of insulation and sealing, involve a different approach.
Low-energy strategies, in this case, are often focused in terms of zoning: different temperatures for different rooms, at different times of the day, according to their occupancy and needs. That’s important for energy savings, and to get it the house should be designed to have different zones, each one with its own thermostat, to control a motorized duct damper system.
These systems require variable-speed heating/cooling equipment: single-stage furnaces or air conditioners are not flexible enough, and cannot provide the right amounts of conditioned air.
In theory, the system is pretty simple, with each room thermostat constantly reading the temperature of its specific zone, and opening or closing the duct dampers, according to user-defined settings.
In practice things can be a lot more difficult. Variable-speed equipment is more expensive, and requires a sophisticated duct design and system. It's not always easy to get significant energy savings.
Supply duct configurations can vary a lot, as you can see in the image at left (from Energy.gov). They depend on the layout of the house. Just do not forget that they should involve a central location of the equipment, and the shortest possible duct system.
As to air return duct systems, the design can be based 1) on return grills located in central locations or 2) on a set of return ducts, designed to send air back to the HAVC equipment.
The grill system is simpler, and may be designed for zoning (to get “separated” parts of the house, according to different heating and cooling purposes) or to let air to flow. Grill systems can be supplemented by door undercuts or by short "jumper ducts", installed to connect the rooms and to allow air to flow back to the central grilles (see image from Energy.gov).