I already wrote earlier that regions with tradable ressources tradable offer a high ROI if the circumstances like enough trade are right. They should get priority for upgrades and also for building slots. The same goes for fish, grain and gold regions, as they can offer considerable positive modifiers.

So if you need lots of food you will go down the grain farm chain and which better place to built your fields then a Grain region? Level IV is not all too often a good choice, but in those cases it's often a great city upgrade.