IMO,

most important is how many castles you have versus how many cities you have. Castles that are 3~4 or more provinces away from the closest common border with a foreign faction should be turned into cities.

secondly is naval trade. Don't bother to construct ports in castles for any other purpose than ship production. Ports and naval merchant constructions in cities are on the other hand an awesome source of income, so make sure you have built the best port avaible.

third is the farms, which provide about as much income in desolate regions as trade does. Also they increase population growth which again leads to new upgrades of ports and farms and more income.

lastly there is the tax rate, which I usually have set as high as possible. If you have a city that was created huge by always having low/normal tax rates, you might suffer problems with popularity as when spies enter or if you get excommunicated or similar since you cannot lower the tax rate much. I don't know if it is more profitable either.