On occassion there are a thousand passengers at some stops. There is over 50,000 wood/planks at some of my warehouse stops..would that make a difference?
It's actually not the number of passengers / amount of goods, but the number of aggregation items which are grouped according to the destinations of passengers/goods. For goods of a given category, there are usually very few destinations and valid routes, so this part should hardly matter. For passengers, there is often a big interconnected network with many stops, so there it will matter.
My ships..and I suspect there are well over 300..have a loop route with 19 stops.
Nobody mentioned the obvious, so I will: if you use waypoints between the other stops, at least for longer distances, time for route (re-)calculation may drop vastly.