While it is unlikely they will bag a dozen medals, they are capable of pocketing at least half the target set by the South African Sports Confederation and Olympic Committee (Sascoc), which would be a significant improvement from the 2008 Beijing Games where they secured only one silver medal.
Since he failed to progress beyond the semifinals at his maiden Games in Beijing four years ago, Van der Burgh has cemented himself as a serious prospect to step on the podium in London.
He has been South Africa's top swimmer over the last few years, breaking the world short course records in both the 50m and 100m breaststroke events in 2008.
He also won bronze medals over both distances at last year's Fina World Championships in Shanghai.
Viljoen will arrive at her third Olympics as the number one women's javelin thrower in the world after improving her own national record with a 69.39m heave at the New York Diamond League meeting in June.
She will be joined by South Africa's flag-bearer, Caster Semenya, as the athletics squad's greatest medal hopefuls.
Semenya's national record performance of 1:55.45 to win the world title in Berlin in 2009, and her silver at last year's global championships in Daegu, make her a strong contender at the Games, despite erratic performances over the past two seasons.
Long jump ace Khotso Mokoena, South Africa's only medallist in Beijing, has also been touted as a medal prospect, along with one-lap hurdler LJ van Zyl.
Elsewhere on the track, Oscar Pistorius is unlikely to be in contention for a medal in the individual 400m event, but the double amputee will be one of the drawcards in the English capital.
The fastest one-lap sprinter in the country this season, Pistorius will be joined by Van Zyl, Fredericks, Ofentse Mogawane, Willie de Beer and Shaun de Jager in the 4x400m relay squad as they target a repeat performance of their silver medal-winning effort at last year's global championships.
In the pool, Van der Burgh will be joined by rising star Chad le Clos, who has been talked up as another prospective medallist. Le Clos will compete in the 200m and 400m individual medleys, and the 100m and 200m butterfly events.
He is also expected to be entered in as many as three relay disciplines, which would make him the first SA swimmer to turn out in seven events at the Games.
Meanwhile, South Africa has sent a strong cycling squad, with mountainbike master Burry Stander leading the charge.
The 24-year-old could go into his second Olympic Games as the world's top cross-country rider, depending on his result in the final leg of the UCI World Cup series in France on Saturday.
Women's road cyclist Ashleigh Moolman, who is 23rd in the world rankings and boasts a top-10 finish at this month's Giro d'Italia Internazionale Femminile, will also hope to punch above her weight and step on the podium.
BMX ace Sifiso Nhlapo will be eager to make up for the disappointment in Beijing four years ago when he crashed out of the final in the discipline's maiden appearance at the Games.
While Nhlapo has struggled with his form, due to a spate of injuries over the last few years, the gritty rider remains a strong contender to shine in London.
Canoeist Bridgitte Hartley, who set an unofficial world record last year in the K1 500m race, could spring a surprise, while triathlete Richard Murray also launched himself into contention with a maiden victory in the Triathlon World Series leg in Hamburg, Germany, on Saturday.
South Africa's Olympic campaign starts on Wednesday – two days before the opening ceremony – when Olympic debutants Banyana Banyana square up against Sweden in their opening match of the women's football tournament.
The South Africa team will start their medal charge on Saturday on the opening day of the swimming events in the pool. – Sapa