You're right about the obstructions to the air flow causing more noise. Air gets compressed when it goes around sharp edges, which makes more turbulence and the turbulence makes more noise. More edges means more noise.
You've got the right idea. Make one big hole and put a chrome wire fan guard over it.
One big hole only has two edges (top and bottom) so it makes the least amount of noise. If you can round off the top and bottom edges of the hole and polish the inside of the hole then that would be ideal. Removing the sharp edges removes more noise.
If you can find a fan guard with the fewest number of wires then there's fewer obstructions - also less noise.
A fan with a low dB rating also helps. I'm partial to AeroCool fans. I use them in my case and they're very quiet. They're more expensive than other fans, but have high air flow and they're very quiet. Aerocool Shark 120mm Black Edition
My personal experience with airflow, noise, fans, and holes: DM 2004 case needs way more airflow
-- In this case (pun intended) I got around the front fan turbulence by creating a lot of smaller rounded edge holes that had an overall surface area greater than what the fan needed to stay silent.