Ghana eliminated the USA in the knockout round four years ago to make it to the quarter-finals before bowing out to eventual fourth-place finishers Uruguay.
In South Africa, Serbian coach Milovan Rajevac, with Kwesi Appiah as assistant, steered the Black Stars into the last eight.
But they were cruelly denied a place in the last four when Asamoah Gyan failed to convert from the spot following a handball on the goal-line by Uruguay's Luis Suarez, with Uruguay going on to win the penalty shoot-out.
But with Group G rivals Germany and Portugal widely expected to grab the top two qualifying places, a healthy dose of realism may be required.
Appiah's side features a host of big names who ply their trade in Europe, from Juventus wingback Kwadwo Asamoah to AC Milan midfield pair Michael Essien and Sulley Muntari, Schalke forward Kevin-Prince Boateng and striker Jordan Ayew, who plays for Marseille.
Ghana have also recently welcomed back striker Abdul Majeed Waris, who scored nine goals in 16 Ligue 1 appearances for Valenciennes during a six-month loan spell from Russian side Spartak Moscow, after he returned from injury quicker than expected.