Paint.NET 4.1.6 (Currently the latest) (>100 plugins)
2x Intel XEON E5620
Nvidia Quadro P4000 2GB
Windows 10 Build 17134
Simply, when hovering the mouse over the "Layers" panel, the layer highlighting lags behind the mouse. Selecting/clicking on it has a delay (less than a second but noticeable). I currently have 40 layers with maybe 10 of them with blend mode other than "Normal". The project is stored in .pdn file with being reopened maybe only 7 times. Bug is still present after reopening the project.
If needed, I can search up exactly what plugins I have, most of them if not all of them are from some kind of plugin packs from this website.