I switched back to the 0.4mm nozzle on Friday. Printer is still working flawlessly. The calibration cube pictured above is certainly the best I've seen in weeks.
I think the problems were caused by two separate partial clogs: First after a change from Prusament PLA to Fillamentum NonOilen, the second after I ran the Mini's built-in first-layer calibration (which assumes a 0.4mm nozzle) with the 0.25mm nozzle.