Thus, games are straightforward races of expansion. After choosing one of the dozen or so scenarios set in the US and Europe from the dawn of the railroading age in the 1830s right into the age of the bullet train in the mid-20th century, you're plopped down in a random town. From there you must take your starting stake and lay down tracks connecting your town to both neighboring cities and resource-producing facilities like farms, steel mills, and coals.
It's snap to make a buck by following the rules of supply and demand. All you have to do is check out what the neighboring cities want and/or are processing and then lay down track to get these goods to them. So, for example, if NYC wants ore, you can make a pretty penny by laying track down to connect the city with mines in upstate New York. There are a few vaguely fiddly issues with stocks and buying out competitors, but generally it's all very simple.
You have some stiff competition, though. Sid Meier's Railroads! features hardassed AI railroad barons like Jay Gould and Cornelius Vanderbilt, so you have to stay on your toes. All of the maps are compressed, too, even in wide-open regions like the Western USA, so often they begin their empires in the next town over and you have to race them from the moment that the game begins.
They also provide tough opposition when it comes to buying up industries and patents during in-game auctions. To really max out your profits, you need to buy resource-producing or resource-processing factories, but your rivals know this and will often drive up the price when they come up for auction. It's the same deal with patents. Technological innovations that cut costs show up on a regular basis as the years fly by, and you can bet that your rivals won't let you have them for bargain prices.