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.