As said it depends....
Originally I would've said I liked Moonshell2, due to the 'extensions' it had & how by adding them you increased the functionality of it (although 'skinning' it was a pain - & you couldn't run ROM's from it), but for some reason I also HATED M3 Sakura (but they were virtually the same thing) at the same time - weird
AKAIO/Wood/Acekard OS (they are all similar in design) is also liked for it's simplicity, but Wood has the slight edge as it has more 'features'
And although I have a DSTwo as my main card - I DON'T like how each feature (emulators/DSGame/plugin) has a different menu - if they were all of a similar layout/design then I would be happy - which is why I like iMenu as this allows running homebrew/SNES games & DS games all to be run from the one menu. It's a shame the GBA emulator can't work the same way - but I can only hope someone will release a ARG() version of it (if the source code is ever released)
I've not tried any other OS (well except for the R4i gold '3-icon' layout - but I hated that type)