The idea of this comic is that it's not worth spending dozens of hours (say, over a year) customizing your work environment in order to save just a few hours during that same time period.
There are other factors at play besides the wall clock time. It should be easier to maintain focus and stay in the zone. I like having a shortcut for everything I do on a daily basis so that it can become muscle memory.
Also, consider that sometimes your behavior will change in response to the optimization, for example you may run your tests a lot more often if they complete quickly.
Finally, not all of your time has equal worth. I find that I do most of my work flow tweaking during my downtime.
I think "rezoning time" is the same thing as wasted time. If I have to "zone up" for a task, and that part takes me 30 mins, while once in the task it takes me 15 mins, I figure I've wasted 30 mins.
As for different types of time, I fully agree. If I'm in a half hour between meetings for instance, and I can do some tweaking to simplify actions, I can claim I spent 30 mins on that, but, I can't claim I traded 30 mins of "productive" time for it. So if that 30 mins of work allows me to have a less disruptive action in a workflow, the amount of time that workflow actually saves is hard to measure, and may overall be well less than 30 mins, but who cares? Life is smoother, and it would have been 30 wasted minutes otherwise.
There are other factors at play besides the wall clock time. It should be easier to maintain focus and stay in the zone. I like having a shortcut for everything I do on a daily basis so that it can become muscle memory.
Also, consider that sometimes your behavior will change in response to the optimization, for example you may run your tests a lot more often if they complete quickly.
Finally, not all of your time has equal worth. I find that I do most of my work flow tweaking during my downtime.