I've always been a fan of the canon interpretation that anything other than the two nacelle pattern was because someone needed to compensate for something in the workload. Battleships (Federation-class variants, Galaxy-X) have 3 so one can get chopped off and they can keep on trucking, quads rotate through them to even wear/allow 'sprinting' for longer, singletons being 2 nacelles in a trenchcoat for cost/maintenance reasons (which explains why they're often proportionally oversized), etc.