There's no clear front-runner, though several leading candidates have been mentioned over the years as "papabile"—or having the qualities of a pope.
So, will the papacy return to Italy, after three decades of a Polish and a German pope? Or does Latin America, which counts some 40 percent of the world's 1.2 billion Catholics, deserve one of their own at the church's helm?
Will a younger cardinal be considered, now that future popes can feel freer to resign? Or will it again go to an experienced cardinal for another "transitional" papacy?
The 110-plus cardinals who are under age 80 and eligible to vote will weigh all those questions and more when they sequester themselves in the Sistine Chapel next month to choose Benedict's successor, a conclave that will likely produce a new pope by Easter.
Some said Benedict's resignation presents an opportunity to turn to Africa or Latin America, where Catholicism is more vibrant.
"Europe today is going through a period of cultural tiredness, exhaustion, which is reflected in the way Christianity is lived," said Monsignor Antonio Marto, the bishop of Fatima in central Portugal. "You don't see that in Africa or Latin America, where there is a freshness, an enthusiasm about living the faith."
"Perhaps we need a pope who can look beyond Europe and bring to the entire church a certain vitality that is seen on other continents."
Cardinal Wilfrid Napier of South Africa agreed.
"I think we would have a better chance of getting someone outside of the Northern hemisphere this time, because there are some really promising cardinals from other parts of the world," he said.
Despite that enthusiasm, more than half of those eligible to vote in the College of Cardinals hail from Europe, giving the continent an edge even though there's no rule that cardinals vote according to their geographic blocs.
It's also likely the next pope won't radically alter the church's course, though surprises are possible.
"Given the preponderance of cardinals appointed by popes John Paul and Benedict, it is unlikely that the next pope will make many radical changes," said the Rev. James Martin, a Jesuit author. "On the other hand, the papacy can change a man, and the Holy Spirit is always ready to surprise."
A handful of Italians fit the bill, top among them Cardinal Angelo Scola, the archbishop of Milan. Scola is close to Benedict, has a fierce intellect and leads the most important archdiocese in Italy—no small thing given that Italians still dominate the College of Cardinals.
On Monday, Scola, 71, donned his bishops' miter and appeared in Milan's Duomo to praise Benedict's "absolutely extraordinary faith and humility."
"This decision, even though it fills us with surprise—and at first glance it leaves us with many questions—will be, as he said, for the good of the church," Scola said.
Other leading Italians include Cardinal Gianfranco Ravasi, head of the Vatican's culture office and another intellectual heavyweight who quotes Hegel and Neitzsche as easily, and almost as frequently, as the Gospels. He has climbed into the spotlight with his "Courtyard of the Gentiles" project, an initiative to enter into dialogue with the worlds of art, culture and science—and most importantly atheists.
Veteran Vatican analyst John Allen Jr. has labled the 70-year-old Ravasi as quite possibly "the most interesting man in the church." Raising his profile further: Benedict appointed him to lead the Vatican's spiritual exercises during Lent, giving Ravasi a visible forum in the weeks leading up to the conclave.
Benedict's onetime theology student, Viennese Cardinal Christoph Schoenborn, 68, has long been considered to have the stuff of a pope—multilingual, affable and, most importantly, Benedict's blessing.
He has been dealing, however, with a difficulties in Vienna, where a revolt of dissident priests has questioned church teachings on everything from women's ordination to celibacy for priests. His decision to let a gay Catholic serve on a parish council raised eyebrows among some conservatives, who said the move clearly sealed his fate as too liberal for today's College of Cardinals.
There are a handful of candidates from Latin America—and by Monday their backers were in full force touting their attributes.
"It's time for there to be a Latin American pope, because Latin America has the greatest number of Christians," said the Rev. Juan Angel Lopez, spokesman for the Catholic Church of Honduras. His man, Honduran Cardinal Oscar Andres Rodriguez Maradiaga, however, is considered far too liberal to be elected by such a conservative bloc.
Leading Latin American possibilities include Brazilian Cardinal Odilo Pedro Scherer, the 63-year-old archbishop of Sao Paulo, and Argentine Cardinal Leonardo Sandri, 69, head of the Vatican's office for Eastern rite churches. Sandri earned fame as the "voice" of Pope John Paul II when the pontiff lost the ability to speak because of his Parkinson's disease.
Brazilian Cardinal Joao Braz de Aviz, 65, has earned praise as head of the Vatican's office for religious congregations, even though he's only held the job since 2011. He has had the difficult task of trying to rebuild trust between the Vatican and religious orders that broke down during his predecessor's reign.
His deputy took that effort too far in reaching out to U.S. nuns who were the subject of a Vatican doctrinal crackdown, and was subsequently sent back to the U.S.
Cardinal Peter Kodwo Appiah Turkson of Ghana is one of the highest-ranking African cardinals at the Vatican, currently heading the Vatican's office for justice and peace. But he is prone to gaffes, though, and is considered something of a wild card.
Cardinal Antonio Tagle, the archbishop of Manila, is a rising star in the church, but at at 56 and having only been named a cardinal last year, he is considered too young.
North America has a few candidates, though the Americans are considered longshots. These include Cardinal Timothy Dolan of New York and Cardinal Raymond Burke, an arch-conservative and the Vatican's top judge.
Canadian Cardinal Marc Oeullet is a contender, earning the respect of his colleagues as head of the Vatican's office for bishops, a tough and important job vetting the world's bishops.
Michele Dillon, a University of New Hampshire sociologist who studies the church, said no "radical transformation" is expected in the direction of the church and that a "tweak" here and there would be more likely than an overhaul.
"The church obviously is well regarded for its continuity," Dillon said. "I'm not personally expecting a transformative change, but change is always possible."
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