The German lapped the floodlit Yas Marina circuit with a quickest lap of one minute 41.751 seconds, set on soft tyres, in the evening session after McLaren's Lewis Hamilton claimed the honours in the afternoon with a time of 1:43.285.
Ferrari's Fernando Alonso, Vettel's main rival who is 13 points behind in the standings with three races remaining, was fourth and seventh respectively in the sessions as the team tried new aerodynamic updates to the front and rear wings.
Alonso said it had been "a Friday like any other" with the team testing aerodynamic solutions in the first session and then focusing on tyres.
Hamilton was second on the timesheets in the second practice for Sunday's day-to-night race. Team mate Jenson Button was second and third respectively.
"I think we can be happy with today," said Vettel. "We got a good lap on the soft tyres but in general pace the McLarens were quick and seem competitive, so they're the ones we need to look out for and beat."
Red Bull's Australian Mark Webber, who can be expected to 'ride shotgun' for Vettel in Sunday's race now that he is virtually out of the title race, was fifth and fourth.
Hamilton won in Abu Dhabi last year, after Vettel qualified on pole and then retired with a puncture, and the two men are the only drivers to have qualified on the front row at Yas Marina in three editions of the race.
Such has been their dominance, that they are also the only two to have won the race while Red Bull and McLaren are the only teams to have lapped fastest in the 11 practice sessions held there to date.
Hamilton, who set a best time of one minute 43.285 seconds on Friday afternoon, has been quickest in five of them.
"Our car looked good in FP1 (the first session) but FP2 was a little bit more of a challenge for me," said Hamilton. "It was quite tricky to get a good time from the option tyre, so tonight we'll need to do some work around figuring out how to switch our options on."
Pirelli have brought medium and soft tyres to Abu Dhabi, with one stop race strategies looking attractive given that both are showing good durability.
Vettel, winner of the last four races, was 0.765 off the 27-year-old Hamilton's pace. The double world champion turned the tables in the later session with a lap 0.168 faster than the Briton.
"I don't know. Maybe ask Lewis," Vettel told reporters when asked on Thursday why he and Hamilton had such a great relationship with a glittering harbourside track often compared to street circuits like Monaco or Valencia.
"Maybe he knows the answer. It's a difficult track, a long lap with a lot of corners. A lot of twisty sections. It's not that easy to get it right."
Hamilton has his cousins, children of his late paternal aunt, attending the race and has fond memories of last year when he won the race on his mother's birthday with her watching trackside.
Red Bull can clinch the constructors' title this weekend but McLaren, who are still in contention for that championship, can throw a spanner in the works if they can carry over their practice form to the race.
Hamilton has nothing to lose and is sure to start aggressively while Vettel knows he cannot afford any retirement.
The first session featured a new face in Max Chilton, driving the Marussia for first practice only, but heavily tipped to become Britain's fourth driver on the grid next season.
The 21-year-old was 22nd fastest, a second behind Germany's Timo Glock in the other Marussia.
Finnish reserve Valtteri Bottas took Bruno Senna's place at Williams and had exactly the same time as Venezuelan Pastor Maldonado for much of the session until the race driver popped in a quicker lap.
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