Through the elongated narrow Andean region runs 1 major road: the Panamericana. When you arrive in Quito – many foreign flights go to Quito, then make a domestic flight to Guayaquil to fly back from there – it is best to first explore the northern area of Otavalo and/or the cloud forest of Mindo before traveling south by land.
On the way south, you can visit Cotopaxi (the volcano, the markets and Lake Quilotoa) and then drive via Riobamba (the Chimborazo volcano) and/or Guamote (the Thursday market and villages) via Ingapirca (the Inca ruins) to Cuenca (the colonial city and Lake Cajas). You can deviate from that route along the way to visit the quaint town of Baños or also Chugchilan and Zumbahua with its beautiful indigenous villages. From Cuenca you are then quickly in Guayaquil from where you either fly to Galapagos, visit the southern coast, or fly home.
More info on Andean hotels, Andean excursions or National Parks can be found below