TECHNICALLY if you assume Knuckles to be a common, modern name, it should be "Knuckleses". However, that is not the case with "classical" names, which is basically any name from the old days that ends in "S" (like the previously mentioned Socrates), or last names. Given Sega distinctly went with Knuckles' (simply pronounced Knuckles) Chaotix as the title, they are declaring that Knuckles is clearly named after a classical echidna that likely existed a long time ago in Angel Island history.
Also, as I have now typed this, Ken Penders has an erection, and he doesn't know why.
Also, as I have now typed this, Ken Penders has an erection, and he doesn't know why.