The Greek side claimed the spoils when the two sides met in September, making full use of home advantage to record a 2-0 victory over the Yellow Submarine.
Villarreal are already onto their third manager of the season after Marcelino replaced Pacheta earlier this month following the decision to sack the former Real Valladolid boss, who oversaw five wins, three draws and four defeats in his 12 games in charge.
Marcelino will be content with the start that he has made to his tenure after claiming an extra-time victory over fourth-tier Zamora in the Copa del Rey, before beating Osasuna 3-1 at the weekend.
Jose Luis Morales netted a hat-trick in Sunday's league encounter to help the Yellow Submarine claim their first home league win since getting the better of Almeria in September.
Villarreal will now turn their attention to European matters, with the Spanish side currently sitting in second place with six points to their name, having claimed consecutive victories over Rennes and Maccabi Haifa after being beaten by Panathinaikos on matchday one.
The Yellow Submarine, who have a game in hand over Rennes and Panathinaikos, could secure a place in the Europa League knockout rounds with two matches to spare if they beat their Greek opponents and Maccabi Haifa fail to win in the group's other match.
Having won just one of their four group games (D1, L2), third-placed Panathinaikos have work to do if they are to progress to the knockout stage, although their current position would be enough to drop into the Europa Conference League.
After taking a respectable four-point haul from their first two matches, their hopes of finishing in the top two have been dented by back-to-back defeats to Rennes.
They were edged out via a 2-1 scoreline on matchday three, before they fell to a 3-1 loss on their trip to France, denting their hopes of reaching the knockout rounds of this competition for the first time since 2009-10 when it was known as the UEFA Cup.
Although Panathinaikos bounced back with a 1-0 win over Kifisia before the international break, they will travel to Spain off the back of a disappointing 2-0 defeat to Aris, which represents just their second loss of the Greek Super League season.
Ivan Jovanovic's side will have to quickly put that result behind them because they will be fully aware that another defeat on Thursday would end their chances of securing a top-two finish in Group F.
Mattia Gabbia and Francis Coquelin have returned to training, although it remains to be seen whether the latter will feature in the matchday squad after spending a lengthy spell on the sidelines with an anterior cruciate ligament injury.
After scoring five goals in his last two competitive appearances, Morales is expected to retain his place in the front two alongside Gerard Moreno.
Defender Georgios Vagiannidis has dropped out of the lineup for the last two league games, but the right-back could return to the side after starting the club's previous two European matches.
Villarreal possible starting lineup:
Jorgensen; Foyth, Albiol, Cuenca, Pedraza; Akhomach, Capoue, Parejo, Baena; Moreno, Morales
Panathinaikos possible starting lineup:
Brignoli; Vagiannidis, Schenkeveld, Jedvaj, Mladenovic; Arao, Perez, Gnezda Cerin; Mancini, Bernard, Ionnidis
We say: Villarreal 2-1 Panathinaikos
Villarreal have won each of their last eight Europa League home games, and we think that they will continue that impressive record by claiming a narrow win over a Panathinaikos side that have taken just a point from their two away group games.
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