Argentina, rebuilding after World Cup coach Diego Maradona was let go, scored two early goals in the space of three minutes.
Lionel Messi, appearing marginally offside, chipped brilliantly over Pepe Reina from a through ball by Carlos Tevez, who minutes earlier shot just wide in Argentina's first attack.
Gonzalo Higuain scored the second from a narrow angle after being put through by Tevez, again justifying coach Sergio Batista's decision to field him in a three-man strike force, and rounding Reina.
Fernando Llorente pulled one back from fellow substitute Pedro's square ball into the middle of the box with six minutes remaining before Serio Aguero headed a stoppage-time fourth for Argentina.
"Argentina played very well, we have to recognise that," Spain coach Vicente del Bosque told a news conference.
"It's beneficial to the squad to know how to play the weak teams like Liechtenstein and also the big ones."
"I think Argentina had a lot of merit in preventing (the crowd) from seeing the Spain we saw in the World Cup," his oppositite number Batista said.
Again Villa, looking to equal Raul's Spanish record of 44 goals, took a free kick aimed to Sergio Romero's left.
The shot took a slight deflection on Javier Mascherano at the edge of the wall and beat the diving Romero but hit the post. Gabriel Heinze then blocked Silva's effort from the rebound.
Spain, having made a number of halftime substitutions, almost pulled one back early in the second half when Fernando Llorente headed wide from Jesus Navas's right cross.
