Oh I've longed mused on this.
First, of course - No 'Akiraprise'. My dream design is something like the fan
Icarus class, because it looks beefy enough and can develop into the Daedalus class. The name of the ship should also not be Enterprise: the only Enterprise before the 1701 is the XCV. The ship can still be the first Warp Five ship, but there's definitely Warp Four ones, Warp Three ones before it. Though I also really like the
Aachen.
Bouncing off of the XCV - Humanity in Enterprise as we got it feels so
limited. Barely any real colonies and influence beyond Sol, beyond Earth, other than Terra Nova and the Y-J class freighters. What? How could Enterprise stumble this so hard? There should be a sphere of human space that is well developed.
Reintroduce the Kzin Wars (imagine telling Durga, yes, we had a interstellar war, we beat them, and we spared them, we won't do it to you, that would help a lot with the Xindi if the Man/Earth-Kzin Wars were properly in the 2090s-2130s range). Alpha Centauri, Wolf 359, Sol is actually sort of alone along a sort of ridge that heads spinward (towards Romulan Space) which is why Andoria and Vulcan (Procyon and Eridani) didn't colonize it, letting Humanity do it, but most stars under humanity are poor red ones beyond the Centauri system, but the Centauri system is THREE systems in one, so build those up.
Actually show United Earth and UESPA/Starfleet as fully fleshed out organizations with reach, history, and impact, they're just outclassed. Humanity
may be able to grab Tau Ceti and UV Ceti, though I'm leaning to not, let something else be there to flesh out the show. In the Solar System, show Mars, the Moon, a few asteroid colonies, that stuff. No Vulcan yoke over humanity: Humanity is too far away for them, but they're fast friends due to Vulcan help in the Post-Atomic Horror.
With this built up human space, we can then destroy these colonies and put some weight to conflict there because they're built up.
No Klingons. That's something beyond Andoria, towards the rim, (by my reckoning), Klingons are a 23rd century problem. I don't dislike the Xindi as designs (especially the insectoids and reptillians allowing for stock 'evil' races). Orions, Tellarites, Andorians, Vulcans, Kzin are around and should be seen more, and not always friendly, especially Andorians and Tellarites. Nausicans showing up in the show was a surprise, don't know about them coming around.
Orions are by Van Manaan's star, Tellarites by Sigma Draconis, Kzin at Epsilon Indi. Beta Hydri could be the home to the Xindi analogue, coming up from under sol by Gliese 440 and hitting the Wolf 359 arm. Could be something at Groombridge (Coridian, no, that's 28 ly away, maybe something else - Risa? Why is Risa at Epsilon Cetyi at 79 ly away, anyway?), use real local bubble astronomy to flesh out the bubble and determine routes and potential events.
No Temporal Cold War, Time Travel, no Phase Cannons, no Phasers, Spatial Torpedos, 'Photonic' Torpedoes. Lasers, LASERS, Mass Drivers, Nuclear Missiles, Anti-Ship missiles, anti-missile missiles. Ablative armor was okay, but make it feel more weighty - damage taking more time to fix. Marines/MACO are fine especially as the ship will be running around putting out brush fires.
For the first season, instead of running to the Klingons, the hero ship goes around rebuffing, say, unknown attacks on trading routes and colonies by a new alien pirate power, thinking it's Orion or Kzin, could be the Xindi analogue here or the Romulan analog. I don't really trust a show to be able to show a interstellar conflict off well so I still don't know if I'd want a Romulan War on screen or not - maybe showing the first few battles at the end of the series, maybe, and not with a drone ship but more how Masao did it.
If the show has to show the war, then it should focus on it from the getgo, start at 2155, the ship is the first antimatter ship in the fleet (beyond the prototypes) and its increase in speed, travel time, and power will spearhead the development that'll give humanity the edge over the Fusion-Impulse Romulans. Cut out a lot of fat and needless rubber head aliens we saw in Enterprise until later on when Humanity goes back on the offensive and may need to woo some species, but the core of it should be around the Tellarities, Coridians, Andorians, Vulcans, getting their aid. (Orion sides with/uses the war to prey on humanity more? Kzin-Romulan collaboration/uprising? That galactic south species being a pain, they can hit Alpha Centauri hard - think of them like the Breen in story role. This can allow for combat species and still hide romualn idenity, even if say, there's a Romulan spy posing as a Vulcan, humanity would not find out that they're Romulan, just a 'agent'. I know some novels show the Remans used as slave cannon fodder for the war, but I don't like their design and relately late appearance in the series myself. To keep up the Romulan 'secret', they just let Remans loose? Humanity never confuses them for Romulans, how?)
Just hire Masao honestly. Alarming news come from the spinward way, ships and surveyors disappearing that way, little attacks, then boom, Battle of Hells Gate at the end of S1, early defeats, Romulan fleets that had slow cruised from their space by Xi Bootis are hitting the arm and everywhere, trying to get back to Vulcan - and Sol is in the direct way. Humanity still mostly has Fusion-Impulse ships of its own and at first it's a slug match, colonies burnt, desperation. More BSG in tone at times. That would be different to Voyager for the time but I bet a lot of people may complain it's trying to do DS9 again with a big war. If so, maybe move it back to s2 and have s1 floating around local space, dealing with local powers and colonies and politics to even it out.
Warp is slow between deep space, but maybe warp between systems is faster, the long mused 'warp highways', but still not very fast, this may give a sort of wild west wagon train feel as the hero ship has to go through or at least skim past systems it had gone by previously or find another route.
Show ending with the rise of the Federation after the Romulan war isn't bad. Show off Daedalus coming more into the fleet (but don't automatically mothball the Icarus classes, relegate them to frigate/secondary roles).
Stuff like that.