I swap between the two every now and then, since I sometimes have to use keyboards other than my own that use ISO layout.
Switching between the two is easy enough. Going from ISO to ANSI is easier than the other way around. For example, the left shift is longer in ANSI. But if you come from ISO and still press it in the exact same spot you still hit shift. The other way around (adapting to a shorter shift) is much harder. I would argue that the enter-key on ANSI is also easier to use, even for someone who used ISO before. Yes, it is smaller, but also easier to reach as it extends further toward the middle. It will only take hours (if even that) before you start to appreciate this fact if you are a touch typist.
Other small changes, like the locations of some symbols, are not really a big deal as you do not use the all the time anyway, and you will just adapt over time.