Built a C#/.NET application with support for a serial device. Tested it on systems A, B, C initially, all Windows system, same .NET version, same targeting, same build tool version, same initial connection configuration etc, etc.

Testing - works on A and C, B nopes.
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OK, let's check the source, is there something about B that makes it impossible to execute that bit? - No, there is not, you checked that already, stop poking around, it definitively should work on B.
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OK, maybe admin privileges, there is I/O involved, didn't need that on A and C, but who knows - nope, doesn't work on B.
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OK, maybe something wrong with the connection settings? First try at reinstalling driver - but no, it doesn't work on B.
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OK let's try with another device - more/less devices on B. Other USB ports. No. Still does not work on B.
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OK, this is stupid, but, is the cabling alright? It is, of course it is, stupid - but it still does not work on B.
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OK, at that point I'm just gonna ask a colleague, GrumpySoftwareDev whether he has any clue why it doesn't work on B. GrumpySoftwareDev knows nothing, but discovers that one of his applications doesn't work on Windows 10. You know nothing, Jon Snow, but it doesn't work on B.
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OK, now I'm just going to ask another colleague TheLastOfHisKind who handed B down to me somewhat bluntly if he ever experienced problems when working with B and its serial configuration. TheLastOfHisKind tells me he does not and kindly offers me some input on the situation. Still no progress to get it working on B but he hinted he might have fucked up B's driver. I already reinstalled the driver but didn't reboot, which comes after reinstall.
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OK, I'm just gonna remove and re-install the driver, then restart. Hu! Now the UI is gone but another serial device reacted on a general call. Not fully working on B but we're getting there.
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OK, I don't know, I'm getting frustrated, let's borrow another system D - which has roughly the same configuration as B - from my colleague StrongCurrentGuy. StrongCurrentGuy borrows me his system and cautions me not to break it. I install the driver, plug the device and copy the application from B. It just works on D. Not on B though.
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OK, you know what. I'm done. For shits and giggles I'm gonna remove that driver again, reinstall it and restart, maybe it'll magically work afterwar- WHAT THE HELL, I JUST OPENED IT AFTER RESTARTING, IT JUST WORKS - ON B!

... seriously, what the fuck. But yeah, at least it works now.

Fried two devices today by simply connecting them to a power source.

Changed nothing in the circuitry, no shorts due to solder residues (a simple modification was made), no changes in the input parameters. Check.

The afromentioned devices should have only minor HW changes compared to a previous version I'm working with and as far as I can see absolutely nothing which should cause the damn microcontroller to release smoke like a steam train. (All right, a very miniature steam train.)

So the only significant difference might be the firmware which I didn't check yet but will tomorrow. Not my code and the corresponding IDE just basically sucks. Yay.

On the other hand, the Software part finally feels like I'm getting somewhere. It seems just ... to work. Very suspicious.

Feeling ambivalently frustrated and relieved at the same time. Sigh.