I ran some electric circuit simulation/PCB design software through Wine for a series of courses that actually worked very well. I think the only installation hurdle was installing the Jet database engine (wasn't included with the install). Real-time simulations were a bit slower than they should have been on my machine (no less than some lower end machines I saw, though). Otherwise, it was on par performance and behavior-wise. That has been my most serious use of it, and I found it to be pretty frustration free.
On the flip side, there was an oscilloscope/fgen software interface that did not work at all thanks to some horrible drivers, but it didn't work on 50% of Windows machines either, so I didn't mind too much. There were alternatives in that case.
Indeed configuring Wine to run something can involve a lot from installing different depedencies to .dll overrides. Different configs for different applications are also a bit painful.
For games, I've found using wine though Lutris (https://lutris.net/) to be mostly frustration-free. To avoid the need to toy around trying to find a configuration of wine version, dlls to add/override/etc., and other settings that wine provides, Lutris provides a "recipes" for creating an environment that someone has verified works for the given application. It has a lot of recipes for non-gaming applications as well, although I haven't used it for much of that personally.
Do you use it for serious applications, or mostly just curious if you can manage an iTunes install?
What have you failed to install? What have you succeeded to install, even partially?