In RBY I'd definitely say either Celadon City or Cinnabar Island.
Celadon City is huge and marks the beginning of the most voluminous part of the game. You can now access the Rocket Game Corner which allows you to continue the main quest, you can finally access Saffron City once you've bought a drink from the vending machines, which allows you to play through the entire Silph Co. section of the game straight after the Rocket Game Corner if you please, etc.
Cinnabar Island just has a certain atmosphere about it because of its unique music, the fact that it's the only island in the game (everywhere else is either a Town or a City), the Pokemon Mansion with its eerie diary extracts detailing the story of Mew and Mewtwo, and the fact that the end of the game is drawing nearer as you go for your 7th badge.
For GSC I can't really pinpoint a town or city in particular because they're pretty much all equally as great as one another in my opinion. Ecruteak City is the same as Celadon City in that it gives you a choice of which direction to go in, as opposed to being stuck on a set route, so if I had to choose just one from Johto it'd be Ecruteak City.