Just a slight clarification...there is no elevational head loss. You still get losses from the pipes, elbows and other fittings...normally minor factors in comparison to elevational head loss. Here is a
tool to help you determine if head loss might be a concern.
I had a closed loop on my 50. It worked out okay. I was always a little nervous with that many holes in the back of a glass tank. You won't have as big of a concern with an acrylic. I doubt I would go back to a closed loop with the variety of awesome, low profile, high flow, energy efficient power heads on the market now.
To answer a couple of your questions, you should have more than one inlet if you can, or at least a tee inside of the tank on the inlet. This will help keep the inlet velocity from getting too high and sucking livestock into the closed loop.
Sizing of piping depends on the flow you want to achieve.