The Spaniards, beaten UEFA Cup semi-finalists in 2004 and at the same stage of the Champions League two years later, visit rampant Porto in their semi-final first leg on Thursday while Benfica host Braga in an all-Portuguese affair.
Under the leadership of Manuel Pellegrini, who later went on to manage Real Madrid, Villarreal were beaten 1-0 on aggregate by Valencia in 2004 and by the same score against Arsenal two years later.
However, the Europa League semi-final looks like it could produce goals given Porto's 10-3 demolition of Spartak Moscow in the quarter-finals and Villarreal's 8-2 rout of Twente Enschede.
The match also pits two of European football's most prolific scorers against each other. Porto's Colombian striker Radamel Falcao is the Europa League's leading scorer with 11 goals while Villarreal's Italian forward Giuseppe Rossi is one behind him.
Porto have already been crowned Portuguese champions having won 25 and drawn two of their 27 matches so far, leaving them 19 points clear of Benfica. Andre Villas-Boas's team have been equally formidable in Europe with 12 wins in 14 outings, including all seven away from home.
"I think they're the favourites because they are winning titles," said Villarreal midfielder Bruno Soriano.
"We have to improve our defence to not concede as many goals. If we can do that, we will have taken a big step forward. A 3-2 defeat against Porto would not be a bad result."
However, Porto's form against Spanish teams is uninspiring with only 11 wins in 34 attempts.
Braga's European adventure began last July with a qualifying round tie against Celtic.
