If your turnover rate in the tank can be achieved with two drain lines. Then reducing the number of drains would be ok. It all depends on the size of the holes and how many gallons per hour your pump will be pumping. The overflow box is designed to let a certain amount of water flow out. The size of the bulkheads allow a certain size of pipe which restricts how much water can flow out. As examples: On my 220 I have two drains and two returns. The 2 overflow boxes on this tank only allow 700 gallons each to exit the tank, I had to make sure my return pump would not pump more than that or I would have to have a valve to restrict the flow on the pump. Not all pumps are controllable in this way. On my 600 I have one continuous flow drain line and one backup drain line so that I can have a splashless overflow. The size of the drain line on this tank is 2" pipe and I pump about 5200 gallons per hour. Hopefully this will help you in your decisions.I'm setting up my new tank and have four returns and four overflow holes. Is it ok to plug the four holes in the tank and use 2 of the overflow holes as a return to the tank? Size of the is 96x24x26 (250 gallon)
There are a lot of useful calculators on the reefcentral website that may help you with pluming.