Real Madrid's fading title hopes were handed what could have been a knock-out blow as the stuttering champions slumped to a 3-2 defeat at Malaga to fall 16 points behind Primera Division leaders Barcelona.
Substitute Roque Santa Cruz struck twice in three second-half minutes to help fourth-placed Malaga heap the pressure on Madrid coach Jose Mourinho, who created a surprise by dropping captain Iker Casillas from his starting line-up.
Madrid dominated the first half but were unable to turn their possession into goals and were made to pay as Isco put Malaga ahead in the 48th minute. A Sergio Sánchez own goal drew Madrid level midway through the second half but Santa Cruz secured victory despite a late goal from Karim Benzema.
Barcelona gave stand-in coach Jordi Roura a winning start as goals from Xavi, Lionel Messi and Cristian Tello downed Real Valladolid 3-1.
Roura is deputising for Tito Vilanova, who was discharged from hospital on Saturday after undergoing an operation on his parotid gland on Thursday, and saw his side take a 1-0 interval lead when Xavi tapped in Jordi Alba's cross.
The Spain midfielder then set up Messi for his 91st and last goal of an extraordinary 2012 and, after Javi Guerra pulled one back, Tello rounded off the win in injury time.
Mallorca got their first win in 15 games in all competitions as they came from behind to beat Champions League-chasing Real Betis 2-1 at the Benito Villamarin.
Benat's free-kick had given the hosts an early lead, but Victor brought the Islanders level with a fine header on the half-hour mark.
And the comeback was completed just two minutes into the second half when Mario's challenge on Victor was deemed to have taken place inside the area and Javi Marquez comfortably slotted home the resultant penalty.
Apono and Helder Postiga were on target as Real Zaragoza ran out impressive 2-0 winners on the road at Athletic Bilbao.
Zaragoza had won just one of their last five coming into Saturday night's game but looked in fine form as they eased to the three points courtesy of Apono's penalty and Postiga's effort shortly before the interval.
Granada secured only their second win in seven league games with a deserved 2-1 victory over Osasuna at the Reyno de Navarra.
Nino had fired the hosts into an early lead with a looping header from Raoul Loe's flick-on, but Granada dominated thereafter and should have been level well before Diego Mainz did find the back of the net from Dani Benitez's free-kick four minutes before half-time.
And Benitez himself then put his side ahead two minutes into the second period with a wonderful left-footed strike from outside the area that left Andres Fernandez helpless.