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.
SANTA MARTA - TOLU
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.
AREQUIPA - CUSCO
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.
BOGOTA - VILLA DE LEYVA
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!
Hey folks, this route is so heavenly and exotic, and still so undiscovered, you've got to get on it before the tourism machine gets here.
If you're going to Peru from Ecuador, 99% of travelers will go through Huaquillas, but why follow the crowd? There are at least three other side doors, and all of them are way more cool.
Go a bit east and over the border through Macará, a rice growing capital of Ecuador and also famous for Seco de Chivo, which is a delectable stewed piece of goat in a gravy over rice.
But way before you get there, you can stop first in Balsas, which has a grotto of medicinal waters surrounded by cinnamon and oak trees. Heal thyself, baby!