Guardiola, the former reserve team coach who replaced Frank Rijkaard after Barcelona finished a second straight season without a major trophy, swapped Thierry Henry with Bojan Krkic in the 62nd minute, but the 18-year-old Spaniard headed wide soon afterward.
Villarreal midfielder Marcos Senna, who helped Spain win the European Championship two months ago, gave Villarreal a 54th-minute lead with a free kick from the edge of the area.
Villarreal defender Diego Godin was ejected for fouling Osasuna's Masoud Shojaei, and Javad Nekounam converted the resulting penalty in the 68th.
Osasuna then had defender Miguel Flano sent off for a 77th-minute foul.
Atletico, which reached the Champions League group phase for the first time in 12 years, gained an emphatic victory over promoted Malaga, which made the team the first leaders of the new season.
Defender John Heitinga deflected Tomas Ujfalusi's volley in the 26th minute for his first league goal since his offseason move from Ajax.
Striker Diego Forlan culminated a swift counterattack with a low angled shot to double Atletico's lead in the 38th and then converted a penalty five minutes later.
Substitute Florent Sinama-Pongolle, who joined from Recreativo Huelva in the offseason, added the fourth goal in the 81st.
Gijon's first game in the top flight in a decade ended in disappointment. The team fell behind after Juan Angel Albin's free kick in the 15th minute, with midfielder Diego Castro equalizing with a left-footed shot 20 minutes later.
However, Getafe won the three points after Javier Casquero's 87th-minute strike.
Santander, which finished sixth last season, spurned a golden chance when Ezequiel Garay's spot kick was parried by Sevilla goalkeeper Andres Palop. Garay signed for Madrid in May but has been loaned back to his former club this season.
Santander paid for the miss when Sevilla striker Luis Fabiano, the league's top scorer last season, struck in the 71st.
Santander leveled five minutes later through a header by substitute Juanjo Exposito.
Bilbao began the season in poor fashion with a heavy loss to Almeria. New signing Hernan Pellerano scored for the visitors in the seventh, with Alvaro Negredo and Juanma Ortiz adding goals in the 33rd and 50th.
Bilbao scored a consolation goal through substitute Ion Velez in the 57th.
Betis also made a disappointing start to the season with a home loss to Recreativo, which scored through striker Adrian Colunga in the 36th.
On Saturday, Valencia beat Mallorca 3-0, and Espanyol edged Valladolid 1-0.
(Agencies via Shanghai Daily September 1, 2008)