One of the things that can help to unify the feeling of your layout is to pick a theme. What this means is that you pick a time and place where your railroad operations are occurring. This can be as specific or generic as you want. It can also be as realistic or fictional as you want. As with everything on a model railroad, it's entirely up to you.
This first part of the theme is the location or region where your railroad is located. The first approach to this is to make it generic. For example you might say: "My railroad is based in the southwestern United States". If this was your theme, you would select landscapes such as mountains and cliffs, desert and cacti.
The second approach is to make it specific. Your theme might be: "The 22 mile stretch of the Indiana & Ohio Railroad between Columbus, Ohio and Lancaster, OH". This theme would consist of single mainline track, with a few sidings and turnouts, not a great many industries, no passenger service, and which has a yard at one end, a small town in the middle, and runs alongside a 4 lane divided highway for about half it's length. And the trains are short locals with a dozen or two varied freight cars.
The advantage of a specific theme is that it brings a familiar feel to your railroad. It also gives you a specific list of industries and locations that you can incorporate into your layout. It doesn't mean you need to copy everything foot for foot along your prototype route. But including a few of the locations in relative positioning to each other can replicate the feel of traveling along that route.
The third approach to location is to create a completely fictional area. When you do that you have no limitations on what to include. If you want a northeastern city to flow directly into a desert or jungle, it's entirely up to you. If you want a French TGV traveling on a track next to a Union Pacific freight, that's your choice. And to be honest, that's the route I take.
The second part of the theme is the time period. Again, you can make it as generic or specific as you want. Some people say they're running the Steam Era. Some say they're running the 1950's. And some say they're running April 18, 1972. The purpose of choosing a time period is that it helps you limit your choices in locomotives, rolling stock, and scenery.
Time period can also affect your location theme. Looking at the Indiana & Ohio example from above. If we were to change the time period from modern times to 1890's, then that same stretch of railroad is the Hocking Valley Railroad. It's double mainline track, passenger service is common, and most of the freight traffic are coal trains running from southeast Ohio to Columbus and northern Ohio and the Great Lakes 4-5 times an hour.
If you're like me, however, and want to see a UP Big Boy running next to a Japanese Shinkansen, you can also pick "all time periods". Then again, given the prevalence of railroad restorations and scenic railroads in today's world, it's entirely possible to see old steam locomotives running side by side with modern freight trains.
As an addition to choosing a time period, you can choose a season of the year. Are your trains running in the snows of winter or the oranges of autumn? This will help you make your scenery choices. If you've got a little bit more space, a larger railroad can easily lend itself to multiple seasons. One area might be fall, another winter and so forth.
In the end a theme can be a useful tool for unifying the feel of your model railroad, especially if your goal is to emulate prototype operations for some area and time. By no means, however, feel like you have to tie yourself to that even if you pick a specific theme. Do what feels right to you. If you want to run trains from every continent and time period together, do it. Just have fun!