When I booked a LCY-JFK-LHR redemption ticket last month I used a GUF to upgrade the return leg to F (very inefficient use, I know!) and the Avios needed went down because the outbound was then priced as a WT+ redemption. I queried it but the agent was quite explicit that the calculation was correct and I was entitled to some benefit from the GUF even on the LCY to JFK route. So I imagine it is or at least could be the same for other upgrade instruments.

What I don't think is possible any more is pricing a WT+ ticket in cash on the City to JFK route and upgrading with Avios.