Not everything makes a difference. Some tweaks make a difference in some systems, not in others. That's not imagination, it's experience. And of course, some tweaks may not make difference at all, indeed.
Well, to be honest, it would depend on what tweaks you think make a difference. Since audiophiles can easily imagine differences, and I can find a testimony for any tweak out there, I hope you'll understand - especially as a scientist - that I'm not apt to just take your word for it
As for "known engineering and science", I would be careful with that. I am a scientist myself (a biochemist), and as such I know that we don't know all there is to know and that our current measurements do not reveal all there is to know.
Ok, but scientists are also supposed to have humility in regards to recognizing their narrow scope of knowledge. So the fact you are a scientist doesn't necessarily mean you know what is known, or not known, in the realm of audio, psychoacoustics etc.
I mention this because it's incredibly common for audiophiles who believe in various tweaks to say "We don't know X about audio" when what it really means is "I don't know X about audio." They are just not aware of what IS known. I'm not saying I know this to be true for you, but the "there's a lot science doesn't know" is a common red flag for mumbo jumbo and pseudo-science.
Only cocky engineers lacking a scientific mindset think that we know how to measure all there is to measure.
The engineers don't need to know everything possible there is to measure, to know enough that many audiophile claims are highly implausible, or flat out impossible. Again...it all depends on the claim.
Since you are a scientists you should recognize this basic issue: before assuming "we need to explain X" you should be able to demonstrate "X" exists. So in other words, if a homeopath says "science really needs to explain how homeopathy works!" they are begging the question, cart before the horse. They would first demonstrate homeopathy works - produces statistically relevant results - in a scientifically rigorous fashion, before science "needs" to do any such explaining.
Likewise, when audiophiles say "well, maybe one day science will explain why I hear what I hear when I swap my USB cables" that's also question-begging: a scientist would recognize that one should be able to demonstrate that phenomenon, with some scientific rigour, before assuming it actually exists, and "might be explained some day." (This pertains the more we are in to the realm of "extraordinary claims" - in the case of audio, technically implausible or un-demonstrated claims).
A little humility is advised.
I couldn't agree more. I try to stay in my lane in terms of technical expertise (I'm in pro sound, but I'm not an electrical engineer etc). I also try to stay humble regarding the perceptual liabilities I share with every other human being, and scale the confidence of my beliefs to the plausibility of a proposition. I realize I'm as prone as anyone to imagine differences that aren't there. (And blind testing numerous audio devices has been very educational).
Can you tell me: do you share the same humility regarding the tweaks you think make a difference? That is, if you seem to hear sonic differences in a tweak you are aware is controversial, do you take in to account you could be imagining it?
Cheers.