The impressive margin on a sunny morning at the Circuit de Catalunya further underlined the Briton's status as the man to watch after three wins in a row.
Championship leader Nico Rosberg, who is four points clear of team mate Hamilton and had said on Thursday he just needed a "normal weekend" to regain the momentum, suffered a cooling issue that cut short his session. He was fifth fastest.
Quadruple world champion Vettel, who had a miserable pre-season test in Spain and has had a difficult four grands prix since then, kicked off the first European race weekend of the year with another setback.
The German, winner of the last nine races of 2013, was using a different chassis to the one raced so far but he completed just four laps before pulling over with an electrical problem.
Marshals handed him a fire extinguisher as he inspected the car before hitching a ride back to the paddock on a scooter.
"We had a full electrical shutdown on Seb's car. We're not sure what caused it. It cut the radio and everything," said team principal Christian Horner.
Although the car was returned to the pits, the problem prevented Vettel from taking any further part in the morning session.
Red Bull tweet: Due to an electrical problem that has damaged the wiring loom of Car No. 1, Sebastian will not be able to take part in FP2... #SpanishGP
His Australian team mate Daniel Ricciardo, who has outqualified Vettel in three of the four races and passed him in the last two after the German was instructed to let the faster car through, was third fastest.
Ferrari's Fernando Alonso, the local favourite for his home race after winning last year with plenty of banners in the grandstand urging him on, was fourth on the timesheets.
With the opening long-haul races in Asia and the Middle East out of the way, all teams have brought updates to their cars and Friday's practice sessions were being closely watched for any signs of change in the pecking order.
In a bizarre early incident, a wing mirror on Sergio Perez's Force India broke off and was left flapping around on a wire. The Mexican completed the lap with it in his hand.
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- Jenson Button
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- Circuit de Catalunya