I just installed a new font with ligatures and I was pleasantly surprised to see that Paint.Net supported them fully. I am sharing this information because I did numerous searches before I bought the fonts to understand if the glyphs would display correctly in Paint.Net. The only information I found on the topic was many years old and speculated that I'd need Photoshop or some other design software to display the ligatures correctly.
The font is Gillian and for $30 it was a breeze to install and get the look I was after in Paint.Net. I hope this may help someone else down the road.