On that occasion, United were en route to their third Champions League final in the space of four years, but now they are a team in crisis after a string of damaging developments both on and off the field.
Valencia have also had their difficulties in the meantime, though, and only just picked up their first win of the season at Real Sociedad on Saturday.
Here, Sports Mole looks at how the La Liga outfit could line up against United.
Valencia have been buoyed by the news that Jose Gaya has returned to training and the one-time Arsenal target should be restored to the starting lineup on Tuesday after being replaced by Toni Lato at the weekend.
Kevin Gameiro opened his account in that match and will hope to have done enough to keep his place ahead of Rodrigo Moreno to partner Michy Batshuayi up front. Rodrigo has already scored at Old Trafford, though, doing so in a pre-season friendly in 2014.
The versatile Daniel Wass could also come into the side after being rested at the weekend, although Marcelino is likely to keep changes to a minimum following their first win of the campaign.