I can think of two big improvements to desktop GUIs:
1. Incremental narrowing for all selection tasks like the Helm [0] extension for Emacs.
Whenever there is a list of choices, all choices should be displayed, and this list should be filterable in real time by typing. This should go further than what Helm provides, e.g. you should be able to filter a partially filtered list in a different way. No matter how complex your filtering, all results should appear within 10 ms or so. This should include things like full text search of all local documents on the machine. This will probably require extensive indexing, so it needs to be tightly integrated with all software so the indexes stay in sync with the data.
2. Pervasive support for mouse gestures.
This effectively increases the number of mouse buttons. Some tasks are fastest with keyboard, and some are fastest with mouse, but switching between the two costs time. Increasing the effective number of buttons increases the number of tasks that are fastest with mouse and reduces need for switching.
I use Emacs as my daily-driver so point well taken wrt incremental drill-down though I'd argue that's not just a "desktop thing". You see that in the Contacts manager of every smartphone.
I see "mouse gestures" as merely an incremental evolution for desktops.
Low latency capacitive touch-screens with gesture controls were, however, revolutionary for mobile devices and dashboards in vehicles.