Though I'm intrigued with the 22nd century, the Romulan War, and the birth of the Federation, if I had my druthers, I would've set the prequel show on Robert April's Enterprise.
Regarding the look of the show, I might have 'cheated' and jazzed up the Enterprise and some of the tech to keep in line with modern sensibilities.
Ya beat me to it.
The advantages of the setting would be a familiar setting, a minimum of having to reinvent the wheel with regard to production design, and enough time between this show and TOS to have an entirely new crew. In fact, I could take my "Strange New Worlds" submission and rework it into a pilot very easily (start off with Capt. April fighting back the Klingons at Donatu V, thus earning him the command of a shiny new USS Enterprise).
Of course, it might be seen as a bit too fanwankery for casual viewers, but it's not like ENT did much better on that front, so what the hell...