Manchester City do not have United's experience of toughing things out on European evenings where even the top sides can wobble after hitting unforeseen bouts of turbulence.
But Roberto Mancini's side will hope they got their wobble in early - held at home by Napoli and losing to Bayern Munich which led to the exile from the first team of Carlos Tevez.
And the Blue Moon has been rising ever since with Mancini's men having destroyed United in last week's Manchester derby but equally significantly edging out Villarreal thanks to an injury-time goal from Sergio Aguero to reignite European dreams.
An ideal scenario would be to complete the double over their Spanish rivals, who have yet to register a point, and hope Bayern can send Napoli packing in Bavaria, allowing the Blues to leapfrog the Italians by two points.
A draw in Italy on matchday five would put City on the brink of qualification - even if Bayern provide a stiff final group test in Manchester.
With Tevez still seemingly in City's out-tray for his Munich misdemeanours Mario Balotelli is reaping the rewards of more playing time - witness his brace in the humiliation of United - and he is likely to start at Villarreal after completing a three-match European suspension.
"Mario has experience of the Champions League with Inter and I think he could be important against Villarreal," noted Mancini.
While Bayern and City's group looked tough when the draw was made 2010 champions Inter Milan ensured by losing to Trabzonspor that if they went through to the last 16 they would do it the hard way.
Despite dismal league form - Inter's home loss to Juventus on the weekend left them in the bottom four - new coach Claudio Ranieri has managed to turn things around in Europe and two straight wins have lifted the Nerazurri into top spot in Group B. Inter now meet French champions Lille.
However the French side have gleaned only two points - notably throwing away two more in allowing CSKA Moscow to come back from two goals down to rescue a draw in France.
A win for the Italians will put them firmly in the box, particularly if the match between Trabzonspor and CSKA produces a decisive outcome to leave the loser five points off Inter.
Elsewhere, Real Madrid, who have endured a decade since their record ninth triumph in 2002, will be out to push Lyon towards the exit with a win at the Stade Gerland.
Jose Mourinho's side have yet to drop a point to open up a five-point lead over both Lyon and Ajax, who face Dynamo Zagreb, three defeats already to their name.
Real have injury doubts concerning Kaka and Alvaro Arbeloa after the win over Real Sociedad which left the meringues top of La Liga.
- AAP