Okay, yah yah, I know, this route is pretty short. You can get to "VdL" as they call it in just a few hours. However, there's so much in between that I'm recommending this route as one to get off the bus a lot, stay overnight even instead of going back to Bogota.
First, you want to stop in Chia (no, not to get Chia pets), an idyllic town on a beautiful lake with beautiful courtyards. City folk love to go to Chia for the weekends and chill. Then continue north to Zipaquira, one of my favorite towns in the whole country. The main attraction is the Salt Cathedral, a huge underground mine that has been converted into a church. But the town itself is a charmer too!
Leaving "Zip" on the way to Tunja, you should get off to visit the several important monuments at the site of the Boyaca Bridge (Puente de Boyaca), which is the decisive location where Colombia won its independence in 1819.
Tunja is the chilly and high capital of the province, a major transporation hub, and very important historically. It hosts many festivals throughout the year, so don't be too rushed to pass it by. The colonial architecture and art of the city is both unique and undervisited, so enjoy it without the tourist mobs.
Villa de Leyva is a grand attraction for many reasons. I frankly think it's become overtouristed, but the cobblestone streets and arched alleys have a way of enchanting you no matter what. The town boasts the largest colonia plaza in Colombia, large enough to hold an annual kite festival!
Around VdL is enough stuff to last you for a week! Raquira is a village famous for its colorful pottery and brightly painted houses. El Fósil is a nearly complete fossil of a chronosaur. El Infernito, is an ancient sacred indigenous site in which the grounds are studded with giant phallus statues (that's right, penises). Convento Santo Ecco Homo, is a beautiful monastery founded in 1620 in one of the most perfect climactic valleys you won't want to leave. Santuario Iguaque is a natural Sanctuary in which you can hike around several high-altitude lakes (all day trip). La Periquera is a camping site known for its 7 waterfalls in which you can take a loop trail down to each waterfall (even rappel down them if you want). Pozo Azules is another beautiful area that features three jewel blue colored lakes. more...
This is such a well-worn route it's hardly worth mentioning, but then again I'm surprised at the number of travelers who take it direct without considering all the lifetime experiences they pass up before they get to Cusco.
For hikers of any ability, the town of Chivay should be your first point of order, because from here you can head out to the unforgettable Colca Canyon, one of the deepest canyons in the world. You don't have to go down to appreciate its splendor. On the way there you'll skirt the Aguada Blanca National Reserve, inhabited by herds of vicuñas and alpacas. One of the best hikes is at the top of the steepest side of Colca Canyon where you come to Condor's Cross (El Mirador), where the biggest flying bird in the world can usually be seen soaring amongst the peaks. There are also some picturesque colonial town around the rim of the canyon, like Yanque, Coporaque, Achoma and Maca.
Continuing northeast, you come into the Caylloma province, that possesses some of the highest satin-sheen lakes in South America like Lago Condoroma. As you come toward Espinar, no doubt you will think you are immersed in scenes of Lord of the Rings with the vast plains and swamps and mystic mountains more...
If you're coming from the splendid beach at El Rodadero in Santa Marta or visiting the Quinto de San Pedro Alejandrino where Simón Bolívar spent his last days, go west young packer on this Caribbean coastal route that involves just a couple hours ride at a time.
While most bypass the big industrial port of Barranquilla, it is South America's second Carnival capital (first being Río de Janeiro) at a much better bargain. It also is a great spot for art deco fans, including the Metropolitan Cathedral and the famous Teatro Amira de la Rosa museum and library.
Before you get to Cartagena, stop for an unforgettable experience at the Volcan de Lodo Totumo, a real volcano only about 30 feet high, that bubbles up lukewarm medicinal mud you can bathe and receive massages in, and then get yourself washed off in the nearby water -- very therapeutic and fun!
Cartagena itself is to die for, what I call the New Orleans French Quarter on Steroids! Old, full of pirate history, sultry and exotic. Sit on top of the old town wall at night with a pitcher of coco-limon and enjoy the gentle ocean breezes, visit the old maritime antique stores more...
This is a splendid route that takes you from the capital (constitutional) of Bolivia through breathtaking highlands all the way to the gorgeous wine country of Tarija.
But before you leave Sucre going south, take a side trip east to what I think is Bolivia's best traditional market town, Tarabuco. On your way there, make sure to stop and walk with the dinosaurs at Cal Orcko, which contains over 5,000 tracks of 294 species of ancient beasts.
Going southward, your major "pitstop" worth spending at least a day in is Potosi, a town of intricately colored doorways and some of the best museums in South America thanks to its affluent history from mining. Climb the little hill of Tarapaya and find a natural thermal hot spring on the top waiting to give you a dip with a great view. Potosi is also a major crossroads for transporation going west to Uyuni.
Before you get to Tupiza, you might be tempted to just get off and do some hiking around the picturesque Laguna Kharachi Orcko, but if not wait to get into town where you'll find lots of outfitters to take you horseback riding or mountain biking through the area canyons and valleys. more...
My sweet spot for happy returns is to actually start this route in Misahuallí, a small town to the east of Tena where monkeys stroll around as casually as the people do. Then head north from Tena to go spelunking in the Jumandy Caves outside Archidona and some beautiful lodges and waterfall walks in nearby Cotundo.
If you want to imagine yourself in legendary adventure of Francisco Orellana and Pizarro to discover the source of the Amazon, hike the famous stone Guacamoyas Trail in Cosanga where they began.
Not much farther up the road is Ecuador's highest falls of San Rafael Falls near Salado, as well as Ecuador's most elusive and cranky volcano, El Reventador.
Great white water river rafting trips await you in the Quijos river region, and the best spot to scout for a local outfitter is Baeza (which is also the connecting point if you want to go back to Quito).
In Lago Agrio, which is mostly the entrance point for hiking into the huge Amozonian Cuyabeno Reserve, try to get there on a Sunday for the street market in which you can see the colorfully dressed Cofán people more...