Okay, this depends on a number of things.
First thing to note - really early on in the game, when your trade tech is low and there are lots of little minors, it's usually not worth trading because your return is low, chance of failure is high and all the little minors will compete you out. However, once the map consolidates a bit, your trade tech hits 3, it's well worth your while. Don't use auto-send, obviously. Concentrate on your own COTs first, then neighbouring ones. Don't just look for COTs with the highest return/lowest costs, look for ones which aren't as competitve (ones outside Europe are great later on in the game, almost to the point of being an exploit because the AI generally doesn't go to them). When your nation's developed a bit more, if you're playing a solid economic game (keeping inflation low etc) then you'll find it easy to maintain 5 merchants in every COT you know, which will give you a great financial return.
If you're getting more merchants than you can afford to send, you might be able to experiment by moving your trade slider toward mercantilism - less merchants, but lower costs per merchant. That can help to make trading affordable early on. You don't want to be stuck in mercantilism for the whole game though.
Another note, trading will be easier under the following conditions: Monarch with high ADM rating, high stability, and high trade efficiency relative to competing nations. If ADM rating, stability, and/or trade efficiency is too stunted, it's barely worth bothering because your chance of success will tend to be lower, and your merchants won't last nearly as long.