Okay, I love the first three, and Yellow is probably my favourite game of them. The Elite 4 was extremely hard, all things considered, and in G/S/C, the Elite 4 was pretty much a joke, and Kanto was pathetic, considering once you could beat the Johto Elite 4, all but Blue would quiver beneath your Pokémon team's mighty fists.
R/B/Y was marred by one huge thing - THE FUCKING INVENTORY. Can't remember what TM06 was? Better boot it up, wait for it to tell you, then hit B if it's the wrong one. You have to keep all your shit in order by your own damn self, and the biggest annoyance was the TM's. Then G/S/C comes along and keeps our shit in separate pockets, organizes our TM's by number, and gives us a bunch more (rather useless) balls and such, making things WAY easier to play through.
I think I enjoyed FireRed/LeafGreen the most (haven't played HeartGold/SoulSilver, because it combined the first 151 Pokémon (though more were available through the Islands and shit), and everything I loved about R/B (not Yellow though, as it lacked an adorable, electrically charged companion), and the streamlined feel of the later games. Ignoring natures and such for maximizing efficiency to a self-castratingly insane level, it made for the most fun I've had with my Pokémon, tied with Yellow.
However, R/B are crushed by FR's mighty testicles, so FR/LG are ahead of R/B/Y in the long run.