We are building a house in Northern California, and need some guidance on ducting runs. Average summer temp is around high 70s low 80s, and average winter is around high 30s low 40s. Here's some info about the house.

The house is on the hillside, including the garage it's 3 story and tug to the hill (so the floors are partially stacked). House size is about 4400 sq ft (not including garage), with top floor being 2100, main floor 2000, and bottom garage level 300 for the mud room.

My plan is to have 2 sets of HVAC equipment, one located in the garage serving the main level, and the other set will either be in the top floor closet, or in the attic.

My thinking is that the ducting for the main floor will be run through the garage ceiling, and have the air supplies and returns on the main floor's floor. However, half of the main floor is on concrete slab. So my questions are:

1. Are ductings through the slab a big no no?

2. If so, would it be fine to have half of the floor with air register on the floor or low on the wall, and the other half go through the ceiling? The slab spans from north side to the south side of the house, and it is on the eastern side of the house. The east side is against the hill, and many windows on the north/south and west facing. What I mean is that I expect the side without the slab to be hotter because of the western exposure.

3. For the half that goes needs to go through the ceiling of the main floor, I am thinking of running a main duct in the inside of the pantry to make it less obvious, since our main floor is a very open floor plan with not much walls to hide big ducting. How big will the main supply duct is going to be to roughly feed ~1000ft area (I suspect main floor will need less heating and cooling than the upper floor)? I just like to get some rough estimates.

4. For the return ducting, this is where it loses me. Do I need one big return in the ceiling for the whole 2000ft area, or can I have a good size return in the ceiling (to save some ducting space in the pantry), and run multiple smaller return register on the floor or low on the wall?

5. Can I run both the supply and return ducts close to each other in the pantry? Is there minimum distance guidelines between supply and return registers?

For my runs from the garage I should be fine since my garage ceiling is like 13ft high, I don't need the garage to have such high ceiling, so I plan to run the ducts through a false ceiling in the garage.

6. For the upper floor, is running through the attic not preferrable? If I dedicated a furnace closet in the upper floor, roughly how big would the ducting need to be (both supply and return) for 2000 sq ft? I want to see how much space I need to allocate for the furnace closet if I were to not put the furnace in the attic.

Thanks for any suggestions and comments! My general contractor says he will do the design (he took some courses), but I definitely need a 2nd opinion from all you HVAC experts!