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but given all things being equal, we should adjust the ISO last, since it essence, it degrades the picture.
Well... all things aren't always equal though. Sometimes we set the ISO first, knowing very well we need to start with a limit on how much degradation we will accept as a result of too low an exposure. Then we set exposure even though it might not give us precisely the artistic effects desired.
For example, event photographers commonly shoot in low light. At one event there might be little motion, so a shutter speed of 1/100 could be sufficient, and that may also allow stoppig down for more depth of field. The first parameter set would have been the highest acceptable ISO. And if something then gets going where it is more important to freeze action, the ISO value is retained, but the shutter speed must be set faster. Rather than increase ISO (a disaster), the aperture is set wider even though it is detrimental. In these cases ISO is set first, it is the make or break paramenter, and it doesn't get changed when the environment changes.
Compare that to shooting outdoor events with a camera such as the Nikon D800, where the dynamic range is high enough that changing from ISO 200 to 400 or even to 800 simply will not affect the image that is saved in a JPEG image format which can only encode about 9 f/stops of dynamic range. In this case ISO would be the first thing to change, rather than exposure. An ISO change has no effect, an exposure change is detrimental.
You are right that there are "too many variables", but as you gain experience and knowledge some of what seems overwhelming now will become "the basics" that you don't blink an eye at. Everyone at any given time has a limit. And you'll notice that those with a lower limit often claim anything above theirs is useless trivia. My suggestion is to make an effort, for the rest of your life, at raising your limit! That's what makes photograph fun.