its important to have the lines connect different zones. so a line only going through a residential area will gain less profit then a line going form residential via leisure via commercial to industry.
in a large city i usually let my lines begin at the trainstation and have 4 lines (2 pairs) each pair servicing about half of the city and each having 1/2 stops per area (residential/commercial/leisure/industry). of each pair one goes clockwise and the other counterclockwise. this way i get profits from those lines
i view these innercity lines as feeders for my railway network and as a way to let the city grow which increase cargo demand and thus profit on the cargo lines