Ok so I have had and used so many different combinations of screens it is kind of crazy but I'll list a few here with my thoughts (I don't game so that isn't an issue). Generally I find the right pixel density for my preference is around 110ppi (1080p@21", 1440p@27", 4k@39"-42").
My current and favorite configuration is 3 screens. A 4:3 Dell 2007FP 20.1" 1600x1200 turned in portrait orientation with Acer 27" 1440p screens on either side of it. I like this because it gives me a single primary screen dead center, portrait orientation for more vertical space since I look mostly at text. 4:3 because a rotated 16:9 at 1080p doesn't have enough pixels wide to display many things correctly and 1440p@27" the top of the screen it too high. Then on the side 27" screens I can snap windows to full half or quarter on either screen depending on need/workflow.
I have run a 4k@42" screen with 2x 1440p@27" above it. I felt like I had to sit on one side or the other of the screen and always snap a window to that side otherwise everything is too wide. The screens above it were only useful for very infrequently used things since it was not convenient to have to look up that high. I do like a large 4k screen and a smaller supporting screen for creative applications. In Photoshop it is great having all your tools and still having a large center work area and all your folders and stuff on a secondary screen.
I tried 3x 1440p@27" all turned portrait. Kinda cool for games if your graphics card can push that but wasn't as good as I had hoped at the time and if it was dedicated to game then just get a single big 4k.
I have tried various other combos in the past too but that was with lower res screens that don't have the workspace per screen I needed.
At one point long ago this was my setup.