In my browsing of the forum, it seems that some people are dedicated to a particular railroad company, while others have multiple companies on their layouts. Right now, given that my parents purchased my son a PRR set, I've been trying to get PRR rolling stock. However, I think I'd eventually like to have a layout that is a bit more modern, and since CSX is big here, I was thinking of leaning in that direction. However, the Florence area was built around the railroad (Wilmington & Manchester (eventually rolled into Atlantic Coast Line through a series of bankruptcies), North Eastern (eventually owned by Southern Railway), and the Cheraw & Darlington (also eventually owned by Atlantic Coast Line)), and I thought it would be neat to model that early period as well if I could ever find trains and rolling stock that coincided with those railroads.
So, what railroad companies do your layouts revolve around? Also, when you run your trains, are you hesitant to mix and match your rolling stock, or do you not care is a UP boxcar runs behind your Santa Fe locomotive?