Start small. There's no reason to build a major mainline all at once. By starting small, you'll be able to perfect each area as you go along rather than using a big brush to paint a swath of landscape and place the industries. In the end the results will be more rewarding.
When I first started back in December 2003, my route which is still in existence today started as four baseboards. As my route grew, I limited my expansion to 6 baseboards a night as I worked on my route after work. This progress was far more rewarding than laying track for 100s of miles then placing trees, buildings, etc. The route grew and expanded quite quickly, something you wouldn't expect, and looing back at these sections, though looking a bit dated, they have some nice ideas in them all without implementing DEMs and other fancy techniques. What this did was to allow me to take my time and think of the uniqueness of the area and integrate and implement things that never happen when you're quickly plopping down trees, buildings, and track. It's as though I took out a fine brush and painted details rather than slopping paint on to big areas to get the job done quickly.
Building routes in general requires setting goals and sticking to a plan, and believe it or not, a purpose for the railroad. Establish a backstory behind the "raison d ‘ être". Railroads don't form out of thin air and are corporate or state/government controlled businesses built to carry goods and passengers. Building a tourist line does give one leeway in this, but in general a railroad maybe built to carry goods across country, or to serve a specific industry, a commuter route, a combination of a freight and commuter route, or perhaps a short line which runs passenger service whether that's a tourist thing or its own passenger service. One of the things that helps with this is to look at books, maps, and photographs. If you find a railroad, abandoned or not, do some research into the route. If you capable of it, visit the location and talk to the locals. This history you gather from the locals can be very rewarding and give you more ideas on what to build.
If you get into topomaps, using TransDEM, look at incorporating a DEM terrain into a fictional route. One of the things I found interesting is integrating a railroad where one never existed by surveying out a route and then carefully integrating the rail line into the surrounding terrain while ensuring roads and existing infrastructure is preserved. This adds a whole new dimension to route building as it introduces additional crossings, towns, and other industry opportunities along the line. When integrating the topo either into an existing route, or doing as I did, ensure the railroad looks as though it's been there and not something slapped into place. This aspect can bring on additional challenges as you work out the route around hills, across valleys, and into various towns along the way.
