However Rudi Garcia's side, who have a game in hand, further underlined their scudetto credentials with a dominant display at the Olympic Stadium which simultaneously highlighted the talents of his young crop of stars.
Captain Francesco Totti was ruled out through injury but the club veteran, present in the stands, was on hand to watch the Giallorossi take command from the outset.
Destro eventually headed the hosts into a 44th minute lead from a corner, but in a lively opening half the 22-year-old was among several Roma players to narrowly miss the target as Sampdoria's defence was overrun.
A deft flick from Gervinho was cleared off the line by Daniele Gastaldello on 26 minutes and then Pjanic drilled just wide of Angelo Da Costa's goal.
Pjanic then swung over a cross that Destro missed by centimetres and the 23-year-old Bosnian forward harried down the right to deliver for Maicon only for the Brazilian to fluff his shot.
Roma missed another great opportunity on 40 minutes when Pjanic sent Kevin Strootman clear but the Dutch midfielder drilled straight at Da Costa.
The hosts had a penalty claim waved away when Shkodran Mustafi handled in the area, but from the resulting corner Destro stepped away from his marker in timely fashion to send a powerful header past Da Costa and into the top corner.
Barely ten minutes after the restart Pjanic doubled Roma's lead with an arrow-straight free-kick which dipped just as Da Costa dived, beating the 'keeper at his right post.
Three minutes later a Roma attack caught Samp's defence unaware and when Gervinho passed to Destro the Italian spun and smashed the ball high into the net.
Samp's chances of salvaging anything from the match suffered a blow when Gastaldello saw red on 80 minutes after a rash tackle on Radja Nainggolan, the defender's second bookable offence.
With midfielder Paul Pogba on the bench, Claudio Marchisio made the most of a rare start to tap home the rebound from an Andrea Pirlo free-kick on the half-hour.
Despite being pegged back seven minutes after the restart when Martin Caceres bundled the ball into his own net, Llorente headed Juve's third from a Pirlo corner to wrap up the points.
A week after conceding a late equaliser in a 2-2 draw at Verona which prompted the cancellation of a scheduled day off for his side, Conte said keeping focus throughout was key.
"It's hard to maintain the same intensity for 95 minutes but we have to because at the slightest lapse in concentration anything can happen," the Juve boss told Sky Sport Italia.
"There are times when any shot can become a goal, so you have to be vigilant with Roma and Napoli coming up behind you."
Napoli's joy was tempered by the 71st minute departure of Gonzalo Higuain after the Argentinian striker suffered a back injury.
"We'll see how serious it is in the coming days," Benitez said, whose side face Swansea in the last 32 of the UEFA Europa League on Thursday.