I'm installing the registers in the ceilings of my 2nd floor rooms and my 1st floor rooms.
The air handler is in the attic above the 2nd floor.
I can put the registers just about anywhere in the 2nd floor rooms. I'm running 6" insulated flex off the AH. I have a ceiling fan in each of the 2nd floor rooms. The attic is not conditioned space and would like the each flex run to be as short as possible.
For the 2nd floor, I'm running the ducts through the 2nd floor closets. I will then run the duct through the floor joists between the 1st and 2nd floor. Running the duct thought the joists will be a PITA.
I'm not going to ask about if these are add-on registers to an existing system or if you've calcuated a manual D for required cfm per room, I'll just say that when I do a new construction home I put the registers 18"-20" off the inner wall and point the grill so that the air is blowing towards the outter wall/windows, to fight the heat load coming in.
Most grills are either three way or four way although some people still use two way, meaning directional. It would also depend on what type of grill you plan on using which could dictate register placement.