Barcelona's Messi, who succeeded Real Madrid's Ronaldo as the world's best player in 2009 and has won the award the past three years, scored once from close range and with a stunning 30-metre free kick, while Ronaldo's pair were trademark clinical strikes from just inside the area.
Both again produced virtuoso performances when it counted, wowing close to 100,000 fans in the stadium and the millions of others watching around the world in what is probably the biggest fixture in international club football.
Argentine Messi closed to within one goal of leading 'Clasico' marksman, Real great Alfredo Di Stefano, with his 16th and 17th goals in his 22nd Real-Barca game.
Ronaldo of Portugal became the first player to score in six consecutive 'Clasicos' with his ninth and 10th strikes on his 16th appearance against Barca.
"I don't know I cannot speak individually," a typically modest Messi told reporters when asked about the Ballon d'Or, the winner of which will be announced at a gala ceremony in Zurich on January 7.
"I don't focus on myself or anyone else," added the 25-year-old from Rosario.
Ronaldo's coach at Real, his Portuguese compatriot Jose Mourinho, was asked about the award at his post-match news conference on Sunday but said he was not a fan of the idea of singling out the world's best player.
"I don't want to have to think about the Ballon d'Or, choosing who is the best in the world should be banned," he said.
"They are two players from another planet," he added.
"I would like one of my players to get the prize, one who was champion in the best league in the world."
Mourinho's Barca counterpart Tito Vilanova had no doubt whom he would select.
"He is still young and we don't know yet what his limits are," he told a news conference when asked about Messi.
"You should see how he trains, how he competes, the desire he has to be better every day.
"I believe we will never see another player of his calibre. He is the best in the world by a long way."
