Ronaldo's sixth-minute goal from a clever Kaka assist was his 28th of the season in the league, putting the Portuguese forward five clear of Barca's World Player of the Year Lionel Messi at the top of the scoring chart.
Santander, who are 18th in the standings, were reduced to 10 men six minutes before the break when the referee ruled defender Domingo Cisma had handled the ball for a second time in the game and showed him a second yellow card.
Benzema's deflected effort made it 4-0 a minute from time to seal an 18th win for Jose Mourinho's side in 19 league matches since the end of September and lift them to 61 points from 23 games.
"The best thing is that we have three more points and one less game to play," Mourinho told a news conference.
"We won without sparkle, but without much effort," the Portuguese added.
"At this stage of the season, winning without suffering and without much effort is the most positive thing."
With Real in such imperious form and unlikely to drop many points, world and European champions Barcelona's bid for a fourth straight domestic title already appears a lost cause.
"It was a great game for us tonight and now we'll try to do the same on Tuesday," the French international told Spanish television.
