You have options. You will need to use both holes in the over flow for draining as you mentioned.
You could use the hole outside the box for returns and use check valves. I have check valves on mine. Regardless of what you do, you will need check valves on the returns OR drill holes in them to break a siphon. If the power fail the water in the return lines will back flow creating a siphon.
Yes, check valves could fail, but an airplane could also crash into your house and then you won't have a tank anyway. I know the odds on one are more likely than the other, but still, come on!
Check valves work best when vertical as opposed to horizontal.
You you plug the holes and drill more in the OF box. You will still need check valves or drill holes to break a siphon.
You could plumb it up the back and over. Mine came with an set up like that for more jets. I'll take a picture of it later. I have to go to work.
There are many more options. It's all person preference.
Okay. I'm going to use the two in the OFB as the filter-drain. The two outside the OFB as the water-change-drain w/ball valve.
Final question- Could I drill holes in the top piece of acrylic to run my return pipes through them. Its going in the wall so the only thing you would see is a bulkhead and two 45 degree elbows shooting water in.