Hamilton has led away the field at the last four races, and in qualifying for the Italian Grand Prix has an opportunity to become only the 15th driver in
Formula One history to claim five in a row.
But Mercedes and Hamilton emerged from practice at Monza sending out mixed messages, as has often been the recent case before they hammer home their advantage over one lap.
Hamilton was quickest in first practice on the hard compound tyre, but was only sixth on the timesheet at the end of the second session when the faster medium Pirelli rubber was given an airing.
Vettel was out on his own because although spearheading a Red Bull one-two, team-mate Mark Webber was just over six tenths of a second adrift, with Hamilton 0.887secs off the pace of the reigning triple world champion.
"It was a smooth-sailing day, the car feels good, and although you always want to go faster, we're not fast enough yet," said Hamilton of his practice outings.
"We're certainly not as fast as the Red Bulls, they are quick, but we are still competitive.
"Hopefully we can pick up some pace because I don't know where Red Bull has a half a second (over the rest). His car must feel incredible.
"At the moment I think Sebastian is going to get pole, but we are going to work very hard to try and stop him."
Vettel, meanwhile, downplayed the significance of his cushion over his rivals, understandably so given how Friday times are often deceiving.
"If you look at it too much it can be a distraction," said Vettel.
"I think it will be a close qualifying with many cars up there.
"It is a shortish lap and there are not too many corners, so not much you can do right, and not much you can do wrong."
Vettel has a 46-point gap over Ferrari's Fernando Alonso, who was fifth quickest, 58 to Hamilton and is 63 ahead of Kimi Raikkonen, who was the best of the rest behind the Red Bulls.
Lotus had hoped a long-wheelbase car would be of benefit this race, but after Raikkonen and team-mate Romain Grosjean - driving the standard car - posted identical times in the second session, the team have abandoned the idea.
As Raikkonen noted: "It doesn't feel much different to me."
The Finn added: "We were a little surprised to be third fastest, but we're still quite far away from the fastest cars.
"There are still some areas for improvement so hopefully we can find more speed for tomorrow."
McLaren will be hoping for top-10 grid slots for both Jenson Button and Sergio Perez after they were ninth and 10th quickest, but will be pushed hard by Force India, with Paul Di Resta 11th.