Depends on your focus. If you are following a prototype then seeing what the prototype its different that if you are not following a prototype. You can get rid of the "foobies" (unprototypical cars), all the cars that are out of era, all the cars with bad paint jobs or bad numbers. You can look at what the prototype had in the era you are modeling, and then reduce in proportion to the prototype.
If you aren't following a prototype then get rid of the cars that are poor runners, cars with bad paint jobs, those with less detail, cars for railroads you don't want or cars that don't match your railroad's industries. If you have more cars of a type that your industries use than can ft at the industries, reduce some of them.
Or.....
Buy shelving or storage tubs/boxes that fit under the layout and store the excess.