Have you ever built a six sided box before? You should plan on making some mistakes. Then that crapload of MDF won't seem so large.
Get a plunge router. It, and a circle cutting jig, will make cutting circular holes much easier.
A box made with three layers of ¾" MDF plus the driver will be extremely heavy – as in get a forklift
.
I strongly suggest going the standard route, one layer on all sides with two on the front. You will have plenty of scrap MDF to use as cross braces.
Thick cabinet walls will vibrate less than thin ones, but will still have panels with the same large surface area dimensions, and the same resonant frequency associated with that surface area. Using cross braces makes for smaller panels with a higher resonant frequency. For a sub woofer cabinet, it will be easy with cross braces to get the panel resonant frequency above the pass band of the sub woofer.