The Scots would have clinched a play-off berth by beating the world and European champions, who had already reached the finals in Ukraine and Poland, but second spot went instead to Czech Republic who triumphed 4-1 in Lithuania.
Spain went ahead in the sixth minute when Villa sent debutant full-back Jordi Alba clear down the left and he crossed for Silva to sweep a first-time shot past keeper Allan McGregor.
"As you can see we have a lot of options," Del Bosque told a news conference. "It's healthy for the group getting everyone involved and having everyone feel useful.
"The season is very long and hopefully everyone will arrive at the European Championship in their best shape."
Spain's victory, their 14th in a row in competitive games since losing 1-0 to Switzerland at the World Cup finals in South Africa last year, meant they completed a second consecutive perfect qualifying campaign with eight wins out of eight.
"Tonight was a tall order but Spain were at the top of their game," said coach Craig Levein. "I am disappointed we didn't get anything from the game but in keeping with the second half of the campaign I see a lot of positives.
"I am enjoying my job. This was a fantastic occasion tonight and being manager of the Scottish national team is something I am extremely proud of."
