The hosts threatened to break the deadlock when Jonathan Pereira diverted a Sariano cross wide, shortly before the Brazilian midfielder opened the scoring on 30 minutes.
Granada were denied what they thought was a clearly penalty minutes before the break, after which former Tottenham Hotspur winger Dos Santos made Villarreal's cushion more comfortable.
This time it was Pereira who found himself delivering the cross and Dos Santos succeeded where his teammate had failed earlier in the match, tapping in from close range for his fourth of the season.
Summer arrival Pina, who joined Villarreal from Real Mallorca in July, completed the scoring with his first goal for his new club, with the impressive Cani again involved in the buildup.
The experienced playmaker provided his second assist of the match as he chipped the ball across goal for Pina to head past Roberto, ensuring that it would be a convincing victory for Marcelino Garcia Toral's side.