I deleted the "define" before the config because it was giving me issues before.
I was ready to say that it wasn't a problem, since the configuration store isn't saved anyway...
But then I remembered the little problem ; the assignations are now wandering somewhere at low level outside of an init block, an potentially not proceeded at all.
But it's just half a problem. Most declaration in "option.rpy" are just a copy of the declaration in "config.py", therefore the value are defined and all. And anyway I really don't see why this would imply the need for a double click to save.
This being said, there's also a thing I noticed recently ; I guess that it started with the 7.4.x branch. Ren'Py do not integrate itself to the OS in the same way he did before. Previously, even if the window wasn't the active one, a click on it was directly interpreted. Now, the first click is to get back the focus, and only the second will be effectively proceeded.
Among the same time, I also noticed few games that seem to be, hmm, "heavy" regarding their save. I mean by this what you said, the need to click twice ; as if the buttons expected more weight and the first one was too light.
I'm not sure that the two are effectively linked, nor how they would be, but you talking about the transition... well, perhaps that it make the screen (not the window, the "screen" with its Ren'Py meaning) somehow loose its focus, and therefore the first click would not save because it's used to give back this focus to the screen.
I insist on the fact that I don't know. I'm just thinking out loud.