The theory I've heard has always been do all the physical changes you are going to do and then flash the resulting configuration. Otherwise, if you do changes after the flash you can throw the effects of the flash out the window.
I know a guy who has 2 dynos. He is kinda OC. He told me it took about a month and dozens of "try this", dyno it, then drive it in the real world sequences before he finally got to a combination of settings that gave results that he could live with on his highly modified engine. When I say highly modified, I'm talking everything from displacement changes to valve train changes to polishing, to .... Probably 3x times what the car was worth but he likes to experiment. And he was changing lots more than the normal flash throttle response parameters and even had good mileage in the end.
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