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Barcelona - Vincenzo Nibali will be seeking his second major title of the year when the mountain-heavy Spanish Vuelta begins on Saturday.
Joaquim Rodriguez, the other favourite, is hoping to claim a first win at a grand tour to round off a long but incomplete career.
The 68th edition of the race was designed to punish sprinters and indulge climbing specialists with 13 of its 21 stages held in the mountains.
The gruelling 3 319km race broken by two rest days will begin with a team time trial in Rias Baixas on the north-western coast of Galicia and ends with a traditional arrival in Madrid on September 15.
Tour de France winner Christopher Froome, who was runner-up in the Vuelta in 2011, reigning champion Alberto Contador, and Tour runner-up Nairo Quintana are all sitting out the third and final major stage race of the year.
That leaves Nibali, who won the Giro d'Italia in May and the Vuelta in 2010, along with Rodriguez as the leading candidates to win the three-week test that will take riders throughout the Iberian peninsula after the 2012 event was limited to northern Spain.
While Movistar's Alejandro Valverde will also likely be in the hunt having won the Vuelta in 2009, Rodriguez enters in good form after finishing this year's Tour on the podium in third place.
The 34-year-old Catalan has yet to claim a grand tour despite finishing the 2012 season as the top-ranked cyclist.
He also was runner-up in the 2012 Giro and third in the Vuelta last year and in 2010.
"I know it's tough to win a grand tour, although I have shown that it's within my reach," Rodriguez told Spanish sports daily AS.
"Winning one before I retire would be the high point of my career.
"It's the difference between having a good career, like mine, and a magnificent one."
Rodriguez said that coming close to winning a major race before has both hurt and helped him.
"You never forget it," said the Katusha team rider who excels at climbing.
"These things take their toll, but they also make you a more mature rider when facing adversity.
"I could now be showing off two major trophies and shooting for a third.
"But the truth is I am still searching for my first."
Following the race's start in the mild weather of the northwest, riders will have to fend off the extreme August heat of southern Andalusia before returning to the northern mountains.
The race's single individual time trial comes in the 11th stage.
Three days later riders leave Spain through the Andorran Pyrenees before entering France for a 15th stage that ends in the Peyragudes summit.
Three mountain stages culminate with a summit finish in the Alto de L'Angliru peak on the penultimate day.
"The Vuelta is a very difficult race this year," said Nibali, who will be supported by his Astana team.
"There are some really important stages, like l'Angliru, that will be decisive for the final classification, and a lot of riders up for the challenge.
"One attack by Contador changed the results of the entire Vuelta last year.
"Stages like that are a little bit extraordinary, but they are extraordinarily difficult as well.
"They happen when everybody is looking for an advantage, and when a team is strong enough to go to the front and do something exceptional.
"I think we have a really strong team, and I think we are going to race extremely well at the Vuelta."
With Froome and Bradley Wiggins out, Sky Team's leading rider is 25-year-old Colombian Sergio Henao.
Other riders to watch include veteran Ivan Basso and Samuel Sanchez, whose Basque Euskaltel-Euskadi team will be eager to have a good showing after announcing last week that it will shut down at the end of this year due to a lack of funds.
Joaquim Rodriguez, the other favourite, is hoping to claim a first win at a grand tour to round off a long but incomplete career.
The 68th edition of the race was designed to punish sprinters and indulge climbing specialists with 13 of its 21 stages held in the mountains.
The gruelling 3 319km race broken by two rest days will begin with a team time trial in Rias Baixas on the north-western coast of Galicia and ends with a traditional arrival in Madrid on September 15.
Tour de France winner Christopher Froome, who was runner-up in the Vuelta in 2011, reigning champion Alberto Contador, and Tour runner-up Nairo Quintana are all sitting out the third and final major stage race of the year.
That leaves Nibali, who won the Giro d'Italia in May and the Vuelta in 2010, along with Rodriguez as the leading candidates to win the three-week test that will take riders throughout the Iberian peninsula after the 2012 event was limited to northern Spain.
While Movistar's Alejandro Valverde will also likely be in the hunt having won the Vuelta in 2009, Rodriguez enters in good form after finishing this year's Tour on the podium in third place.
The 34-year-old Catalan has yet to claim a grand tour despite finishing the 2012 season as the top-ranked cyclist.
He also was runner-up in the 2012 Giro and third in the Vuelta last year and in 2010.
"I know it's tough to win a grand tour, although I have shown that it's within my reach," Rodriguez told Spanish sports daily AS.
"Winning one before I retire would be the high point of my career.
"It's the difference between having a good career, like mine, and a magnificent one."
Rodriguez said that coming close to winning a major race before has both hurt and helped him.
"You never forget it," said the Katusha team rider who excels at climbing.
"These things take their toll, but they also make you a more mature rider when facing adversity.
"I could now be showing off two major trophies and shooting for a third.
"But the truth is I am still searching for my first."
Following the race's start in the mild weather of the northwest, riders will have to fend off the extreme August heat of southern Andalusia before returning to the northern mountains.
The race's single individual time trial comes in the 11th stage.
Three days later riders leave Spain through the Andorran Pyrenees before entering France for a 15th stage that ends in the Peyragudes summit.
Three mountain stages culminate with a summit finish in the Alto de L'Angliru peak on the penultimate day.
"The Vuelta is a very difficult race this year," said Nibali, who will be supported by his Astana team.
"There are some really important stages, like l'Angliru, that will be decisive for the final classification, and a lot of riders up for the challenge.
"One attack by Contador changed the results of the entire Vuelta last year.
"Stages like that are a little bit extraordinary, but they are extraordinarily difficult as well.
"They happen when everybody is looking for an advantage, and when a team is strong enough to go to the front and do something exceptional.
"I think we have a really strong team, and I think we are going to race extremely well at the Vuelta."
With Froome and Bradley Wiggins out, Sky Team's leading rider is 25-year-old Colombian Sergio Henao.
Other riders to watch include veteran Ivan Basso and Samuel Sanchez, whose Basque Euskaltel-Euskadi team will be eager to have a good showing after announcing last week that it will shut down at the end of this year due to a lack of funds.
