No, none at all: agreed, Windows does it more than well enough. I'd consciously avoid windows (lowercase 'w') management software just for that reason: I'm already feeling anxious just thinking of how many programs don't play well.
On the NVIDIA GT 710 (not Quadro), it's just the NVIDIA drivers: I long uninstalled their GeForce Experience bloatware.
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However, it does look like it's something much deeper than Paint.NET. I ran through my programs list and found these applications exhibited the bug:
Notepad++ 32-bit 7.9.1
Paint.NET 4.2.14
7-zip x64 19.00
Most Adobe CC software (latest)
Apple iTunes 12.11.0.26 (does not exhibit hover symptom, but still can click behind)
These programs did not exhibit the bug:
Chrome 87.0.4280.141
All Office applications (latest)
Adobe Illustrator CC (latest; 25.1)
Audacity 2.4.2
Noting your DPI test, I used Task Manager's DPI Awareness. The bug almost always appears in programs with "DPI Awareness = System". The safe applications are set to "DPI Awareness = Unaware" or "DPI Awareness = Per-Monitor (v2)" like Chrome, which is a mix of unaware and per-monitor v2.
I'll run some more tests and see what can be done. But, yes: I think this bug report can be closed on Paint.NET's end as it's not just Paint.NET & Notepad++, but a whole bevy of applications.
Though half of me thinks that it's time to upgrade to 2x 1440p monitors, haha...