GBC to GBA for me. The GBA removed so many limitations that the GBC had (file size, color pallete, detailed sprites, music) and packed all of it into a smaller cartridge.

In terms of tech, it'd probably be GBA to DS. Maybe DS to 3DS, but the one that had the biggest effect on the way games are played and how many more options there were for devs, then it'd definitely be GBA to DS.

In terms of the portion of quality games per transition, it'd probably be GBC to GBA. I guess it's also possible for it to be GBA to DS, but the GBA had a lot of really good games. I think the DS had more, but from the few on GBC to the many on GBA makes it seem the most significant, especially if we look at how well the games have aged.

well the biggest innovations surely came from GBA to DS

GBA to DS.

I'd say the biggest upgrades were going from Game Boy Color to Game Boy Advance, Game Boy Advance to DS and DS to 3DS. The Game Boy Color was nice, but practically speaking the new colour graphics weren't that much more fancy than the monochrome ones on the Game Boy and had much the same low level of detail. But Game Boy Color to Game Boy Advance was like going from the NES to the SNES, the DS leap was big because of all the new tech and the possibility for real 3D games, and the 3DS was a pretty big leap as well.

If I had to choose just one, probably the GBA to DS upgrade.

While I love my 3DS I think it's graphical capabilities are FAR OFF the ones of the 360,
for a handheld still pretty impressive.

Personally Ioved the GBA most because it gave me a nice hardware device to hold (im still not too happy with the second screen on the DS) and all the wonderful games and remakes of games that I played when I was like 9! Awesome thing, best handheld and maybe even console ever (for me).

GBA to GBA SP. Backlit screen made all the difference in the world.

I don't think most people even still remember trying to play like Circle of the Moon or something on the original GBA.