Yeah, I don't really do mains that often because I like to cycle everyone based on context and story (like having Barret during the Corel sections of FFVII) but outside of that, I suppose it would boil down to these people:

Final Fantasy VII: Yuffie & Aerith/Red XIII
Final Fantasy X: Rikku, Yuna and Auron
Final Fantasy XII: Balthier, Ashe and Penelo
Final Fantasy XIII: Lightning, Hope and Fang

Tales of Xillia: Jude, Leia, Elize and Alvin

Borderlands 2: Axton/Gaige
Borderlands The Pre-Sequel: Athena

Mass Effect: Garrus & Kaiden
Mass Effect 2: Miranda & Garrus/Kasumi
Mass Effect 3: EDI & Kaiden (#NeverJames)

Dragon Age Origins: Alistair, Morrigan and Shale/Leliana (Awakening: Anders, Sigrun and Justice)
Dragon Age II: Aveline/Fenris, Anders/Merrill and Isabela/Varric
Dragon Age Inquisition: Cassandra, Dorian and Sera

Mass Effect and Dragon Age really varies though because depending on your main character, any of the above could be rendered redundant. I guess the above are those I would probably take the most often, if class didn't matter. It should be said I didn't really care much for many of the Awakening DLC companions, so that was a tough choice. I liked damn near everyone in DA: II so that was a tough one.