Riding a 22-match winning streak, Serena arrives in Melbourne Park fit, fresh and ravenous.
The second seeded Serb has a relatively kind draw until the quarter-finals.
Bopanna and Qureshi will take on Daniel Nestor and Nenad Zimonjic in the final.
Nadal, No. 4 Murray, No. 5 Del Potro and No. 6 Federer all stacked in the same half.
Del Potro underlined his status as a dark horse for next week's Australian Open.
Djokovic, will bid for a fourth straight title at Melbourne Park.
Del Potro continued his encouraging buildup to Australian Open by reaching semi-finals.
Federer was confident he could revive his career, even if it does not happen immediately.
Bopanna and Aisam-ul-Haq Qureshi progressed to the semifinals of the Sydney International.
World number five Juan Martin del Potro began his 2014 season with a win.
Radwanska had won the Sydney title last year as part of a 13-match unbeaten streak
Svetlana Kuznetsova and Francesca Schiavone crashed out of the first round.
Sania and Cara will now compete at the first Grand Slam, the Australian Open, from Monday.
Top seed pulls off seemingly impossible winners against Roger-Vasselin on way to title triumph.
Serena did not let her misfiring serve stop her from defeating Sharapova 6-2 7-6 (9-7).
Maria Sharapova returned after four months out injured with a completely dominant 6-3 6-0.
Djokovic was watched by his new part-time coach Boris Becker at the exhibition event.
Murray has been trying to lower expectations as he begins his comeback from injury.
Victoria Azarenka also cruised into the last eight,in a match lasting just under 90 minutes.
The Bhupathi-Bopanna combine failed to put up any meaningful resistance.