Well, the experimentation is part of the hobby, really. I have a "go to" build for duals - 2x 26g 2.5mm ID netting .4ohms that I generally throw as a first build into most 22mm atties. That tells me things like air, heat, and squonking characteristics of the atty relative to a known baseline (since I'm very familiar with that build in over a dozen atties).
From there, I experiment to either lessen an affect I don't like or increase one I want. Experience, mostly, guides me as to what to adjust. Everything from heat ramp to air flow to firing temp to flavour/vapor output are in play.
For each setup, I have a goal in mind (factoring in the juice to be used and how I want to use the setup - different for different moods and times of the day).
Now, to your two questions...
Do you have to physically adjust the builds to learn? Yes and no. The basic principles (e.g., lower resistances yield more heat, need more air, produce more vapour; smaller chamber atties generally produce more flavour, etc.) are eminently learnable and applicable. The idiosyncrasies of a given atty or juice or... you... requires experimentation. But rather than be a daunting task, it should be viewed as discovery. I daresay you could try a half dozen different build configurations in a single atty in a day. Maybe a long day, with plenty of vaping to test involved, but achievable.
Could I tell the difference between setups blindfolded? Most definitely. There is no way to get, say, a .3ohm 24g dual setup in a Vector to feel just like a 1.4ohm 30g single coil in a RM2 using any other variables (air, dt, etc) you like.
