If you look at enough different railroads, it seems that many of them just worked their way through the alphabet. Others started out using the first letter of the wheel arrangement's generic name, such a "M" class Moguls. This system sorta fell apart when some wiseguy invented the Mikado.

There was a discussion in another thread about the Southern Pacific's AC-class 2-8-8-2 Cab Forwards (the four-wheel truck under the firebox came later): the AC stood for articulated Consolidation, just as their earlier compound 2-6-6-2s were called the MM class, for Mallet Moguls. Usually, the number following the class letter denoted subsequent models of the same wheel arrangement, but this could also include locos that were exactly the same as the previous class, but from a different builder. Some roads had sub-classes beyond this even. The Canadian National, in 1923, rostered 531 Ten Wheelers, in classes F, G, H, and I, with up to 21 sub-classes, and those subdivided further by a lower-case letter: for example, an H-6-d.
Other roads went even further, adding an "s" or "S" after all of the other letters and numbers to denote locos which were superheated. This practice died out when superheated locos became the norm, usually.
You could learn the classes of the various C&O locos, but they would probably have little relationship to the classes that another road used for the same wheel arrangement. Just like the steam loco itself, their class designations appear to be unique to the road that owned them.
Wayne