Mike,
First a couple of comments on your terminology (just for fun--I see you're structural!). The "air handler" isn't 2-1/2 tons. The dx cooling coil within the air handler and corresponding condensing unit (or heat pump) have a capacity of 2-1/2 tons. The air handler includes a blower and filters (and heating coil or burner if you didn't live in Florida) in addition to the cooling coil. I assume by "perforations" you mean the branch duct take-offs. It's not as if you're going to punch a whole bunch of small holes in the plenum and let it blow the air freely out of these holes!
Anyway, you can use flex duct all over the place if you want. The problem is there's a pressure drop associated with ductwork and the smaller and more convoluted the ducting is (not to mention if it's ribbed like flex duct), the greater the pressure drop. This means that you will start losing desired airflow at the registers (air outlets). The blower (fan) is rated for a certain flow rate at a certain "external static pressure". If the system static is made too large (by excessive flex ducting, etc.), the airflow rate (CFM) will drop off and certain areas which are farther away from the blower will not get adequate air/cooling. That's why you see mostly rigid ducting with only a small amount of flex (if any at all in residential applications).
Anyway, assuming you don't have too far to go, the way you get an equal distribution of air is by making the longer runs with larger ductwork and the closer runs with smaller ductwork--to a degree. The other way (and possibly in addition to the former) is to have each branch equipped with a manual volume damper which gives you a way of balancing the airflow--dampering down (closing off) the runs closer to the blower and opening up the farther runs.
Good luck.
