I prefer connecting industries with trains, so when starting a game I usually create a train route between nearby industries. The route is as long as possible, using the initial money along with most of the loan. The remaining loan is then used to purchase the train for the route. Once the route starts paying down the loan, construction begins on a long distance route between viable industries, crossing as much of the map as possible.
My train routes are flat to allow the trains to move as quickly as possible. This also results in the rail often going through mountains, high over the landscape, or around towns. Depending on the terrain, the cost of installing flat routes can be very high, so having a profitable initial route is important. A long distance route starts as a single rail loop with one or two full-length station tracks on each end. If the source industry increases its output then additional rail loops can be added with up to four full-length station tracks at each end. Often, multiple long-distance routes are necessary to achieve the mission objective. To keep the trains running smoothly, I prefer to keep the train reliability above 50%.
At some point, goods will be produced that need delivered. If there isn't a town large enough to accept them, then I'll build a tram between nearby towns in a desirable location to facilitate their growth. I like to take advantage of the catchment area and include as many passengers as possible with a minimal amount of stations.