Early modern Spain is often cited as cautionary tale, though I haven't done as much reading on Spain as I would like. Imperial Spain certainly was no merchant republic, and I think their trade attitudes reflected aristocratic conceptions that helped drive commerce into the hands of the Dutch. Trade was taxed fairly heavily with few guarantees given to property, while high trade barriers (and social barriers) were erected against non-believers of any stripe. It was a weapon against outsiders, for the benefit of aristocrats, which is what the mercantilism mechanic kind of reflects in EU4. In doing so, Spain reduced both her potential suppliers and consumers, and collected fewer middleman fees.
I do think EU4 nods towards high mercantilism being problematic. Colony independence desire goes up with mercantilism. There's also an event where a choice of trade efficiency (free trade) is balanced against protectionism (mercantilism). Trade efficiency can be more valuable, in my opinion.
Aspirationally, I would like for mercantilism to be more like absolutism is right now: attractive, but also a liability. I actually modded in disadvantages to mercantilism years ago, but the game kept on getting updated, and I lost a bit of patience.
The way you interpret the trade system in EU4 is - to my mind - subjective. You can see trade income as merchants just taking the goods, or you can see this as commercial taxes being levied in your home trade node on merchants who are actually transporting goods further than your own nation; your domestic commercial actors are actually global distributors. Kind of like corporations before they became multinational tax-dodgers.
Of course, that doesn't prevent such corporations/merchants from being horribly exploitative - that definitely happened.