Vettel clocked 1 minute, 41.751 seconds for Red Bull on the 5.6-kilometre (3.5-mile) Yas Marina circuit, .168 seconds quicker than McLaren's Lewis Hamilton, who topped the first practice times.
"I think we can be happy with today," Vettel said.
"Overall we got a good lap on the soft tires, but in general pace the McLarens were quick and seem competitive, so they're the ones we need to look out for and beat."
Hamilton's McLaren teammate Jenson Button was third followed by Vettel's teammate Mark Webber, who was dogged by his power-enhancing system which also failed last weel at the Indian Grand Prix. Webber said the problem this time was different, adding that it was "not a big deal" though it "never helps to miss some running on the track during practice."
The other remaining title challenger, Kimi Raikkonen of Lotus, was sixth, up from 10th in the morning.
Alonso struggled to keep pace for much of the day. He was .836 of a second slower than Vettel and lost time when he went off the track. While Ferrari said it would make changes and had brought in new parts, it appears to be facing some of the same problems it encountered in India where Alonso finished 10 seconds behind Vettel.
"We are pushing hard as we can to bring updates to every race," Ferrari technical director Pat Fry said. "Some of the ones we introduced here seem to be positive ... but clearly we have to improve our performance over a single lap if we want to start from the front row of the grid."
The practice in dry conditions was largely without incident though several drivers briefly left the track and two spun out. Among them was Vitaly Petrov of Caterham.
Vettel has won the past four races to overtake Alonso at the top, and by all accounts has the fastest car on the circuit. He leads the Spaniard by 13 points with three races remaining, followed by Raikkonen who is 67 points back. Webber is a further six points back, and Hamilton another two points back. Each of them has to practically win every race and hope Vettel doesn't finish to have any chance.
Vettel cannot win the title this weekend but another victory and a strong performance at the United States Grand Prix would make it difficult for anyone to topple him. If he wins this year's title, he would join Juan Manuel Fangio and Michael Schumacher as the only drivers to win three championships in a row. The 25-year-old German would be the youngest to achieve that feat.
The team can clinch its third consecutive constructors' title in Abu Dhabi if Vettel wins and Webber finishes no worse than eighth, or the two finish second and third. Red Bull leads Ferrari by 91 points, and McLaren was a further 10 points behind.
Vettel has had mixed results in Abu Dhabi, a day-night race in the desert. He won his first championship in 2010 when he won the race to pip Alonso for the title, but last year he crashed out on the opening lap with a puncture. He secured a milestone pole position a day earlier, tying Nigel Mansell's record of 14 in a season.
Hamilton, who won last year's race in Abu Dhabi, was a favourite for the drivers' title after winning the Italian GP on Sept. 9. But he has struggled ever since, failing to reach the podium in the past four races including the Singapore GP where he retired after leading for almost half the race.
Critics have contended his poor performance might be due to the distraction of his much-publicized announcement that he's switching to Mercedes next year.
Hamilton said he was disappointed to be edged out on Friday by Vettel and conceded it doesn't bode well for his chances of securing pole on Saturday. He said the second practice "was a little bit of a challenge for me" and that "it was quite tricky to get a good time on the option tires. "
"If we get pole it will be fantastic but we shouldn't get our hopes up," he said. "The last three races have been won by a certain guy and that car tends to be very quick around here. If we get ahead, then it will be a huge bonus for us."