I think this is the perfect route for TSW3 as it has a large amount of different vehicle types making it nice for expansions, including various freight workings and passenger services meaning there's a huge variety of gameplay options for all types of people (Read profit making opportunities for Dovetail Games if it motivates the company any further). The route would Start in Crewe and contain both the passenger and freight areas. The line would then take the Crewe-Manchester line towards Manchester Piccadilly. Splitting for the Styal line and the line to Stockport would provide multiple interesting paths into central Manchester and allow Styal line airport services alongside Stockport bound fast services to be played with freight worked between them. Continuing north I would suggest the route terminating stations be Manchester Victoria, Salford Crescent, Eccles and Trafford Park which - though not natural terminating points - would allow the player to traverse the beautiful Castlefield Viaduct through central Manchester and have access to the new Ordsall Chord and Manchester International Freight Terminal. Overall I think the roughly 85km of track with a large number of different operators, modes and diverse landscape would be a great experience for TSW3 players and this route would be extremely interesting gameplay for all that like British trains.
Whilst I would love to see this in game you also have to balance the fact that we have almost none of the rolling stock or assets for this in game right now, so what you'd get is an empty route with one type of stock, and a class 66. Then maybe down the line they'd add in one more stock (and a 66) and that would be it So maybe better to wait until we have a few more stock assets that could be used on these big main lines so they get populated?