I'll admit to only having been to Tokyo about a half dozen times, for up to two weeks at a time. It remains one of my favorite cities, but at the end of two weeks I was ready to go home. I don't usually feel that way when traveling.
I found it lonely for the same reason I loved the city: it was so familiar, and yet so different at the same time. I felt like gears that were slightly out of mesh, not enough to snap, but enough to wear away the edges and cause subtle damage over time.
Making friends as an adult is always hard, but being a transplant into such a new culture is even harder. Everyone was friendly, but finding true connection is difficult: language barriers, cultural differences, biases (on both sides), and perhaps the transitory nature of my stay meant there was always a constant difference.
I always felt like an outsider, even when welcomed warmly. Maybe this was me, but I always knew I was being accommodated: "he's a gaijin, he doesn't know better." This was absolutely kind, but I also knew that I didn't know better, and didn't know what I didn't know, and that created a subtle tentativeness and friction in social interactions.
The classic scenes of Tokyo streets with tall buildings filled with small shops and laced with vertical signage is an apt metaphor for living in Tokyo. There is so much hidden behind the facades that it takes a lifetime to know what's really there, unless you have a guide with infinite patience.
Maybe other cities, or towns, would be different. Maybe it would be much easier if I was fluent, or planned to stay for years. Maybe someone without tendencies towards introversion, or who went with a partner to lean on, would have a very different experience.
But like I said, many small factors just wore on me, and I was happy to return to the warm embrace of home.
I'm afraid I don't know enough about the startup scene to do more than speculate. I was there representing an enterprise software company, which has very different dynamics - especially in Japan.