How big will your model be, and what sort of equipment? If it's large sized and you have a big mix, I'd be partial to a roughly pentagonal model with six main interest areas.
-Pacific Northwest - Seattle and environs (Balmer Yard, Stampede Pass, the Cascades line to Vancouver, bits of the old MILW, and the former SP&S.)
-Upper Midwest - Minneapolis and environs (Northtown Yard, iron ore trains, UP/CP/CN/shortline action, grain elevators, and the former CB&Q River sub)
-Chicago (interchange with everyone east plus shortlines, Metra-contract passenger ops, the Aurora Speedway, Galesburg Yard)
-Gulf Region - Texas and Louisiana (El Paso interchange into Mexico, Fort Worth headquarters and global dispatch, the Houston/Galveston area and New Orleans)
-Southwest - primarily California (Tehachapi Loop and Cajon Pass, the intermodal trade through Alameda, and fresh produce shipment from the Central Valley)
-in the middle: Western Midwest - Nebraska, Kansas and Wyoming (the Powder River coal and gas fields, fast intermodals and the Alliance, Nebraska shops)
If you only have specific equipment, pick one area specifically. (Heavy on GE B40-8s? Best to go with the Southwest/Western Midwest, where they are primarily used. Got a whole fleet of grain cars? Center it around Minnesota.) Otherwise, good luck, have fun, and take Otto's advice about the book!