But the other two in the group, Australia and Chile, can put a spoke in their wheel.
Spain are just about favourites to top the group. The Oranje, with the newly appointed Manchester United manager Louis van Gaal guiding them, performed brilliantly in the Cup qualifiers, the marauding Robin van Persie knocking in 11 goals.
The clash between the two teams could go a long way in deciding the eventual winners of the Cup.
Spain, however, have been off the boil for some time. They were completely outclassed by hosts Brazil in the final of the 2013 FIFA Confederations Cup and lost to minnows like South Africa in international friendlies.
Their narrow, lackluster victories over sides like Belarus and Equatorial Guinea showed they were not the side that took the world by storm in the Euro 2008, World Cup 2010 and the Euro 2012, making them the only national team with three consecutive wins of either the continental championship or the World Cup.
The Netherlands had an exceptional World Cup qualifier, topping the group with nine wins and drawing the remaining one.
The stars of 2010 are still present in the current team - Arjen Robben, Wesley Sneijder and Robin van Persie.
Of them, Robben is still at his best at Bayern Munich, but Van Persie had a difficult season with Manchester United.
The career of Sneijder, who scored five times in 2010, went downwards after the last World Cup. However, he regained some of his magic in the later part of the season at Galatasaray, so he may yet rise to the occasion.
However, the majority of the current Dutch squad are playing in the home league and one can question if the team has enough experience to be battling it out at the highest level in Brazil.
Chile are the outsiders in the group but are very capable of causing an upset.
They have never played the Netherlands, but in their most recent outing against Spain, they managed a hard-fought 2-2 draw.
A win over both Australia and the Netherlands is entirely possible and that could seal Chile's passage into the next round.
The Chileans reached the round of 16 at the last World Cup and world-class players like Juventus midfielder Arturo Vidal and Barcelona forward Alexis Sanchez should make them better this time.
Chile lost only two of 15 games last year, and drew with Spain and beat England in friendly matches.
It's safe to say that Australia are there to make up the numbers this time around. The Socceroos had an up and down qualifying but managed to make it to their third consecutive World Cup.
The buck should stop there for Australia, though, as their lack of international experience and a new coach means they are in transition and should not pose any danger for the rest of the sides.