I guess Plankton would be the main enemy, or perhaps Mr. Krabs due to his cheapness (Not that SpongeBob would care). I'm guessing that the only ENEMIES SpongeBob has (That he has never befriended) would be the Dirty Bubble, ManRay (Before he turned "good"), and the TattleTale Strangler.
It kind of varies. Plankton is the main antagonist, so he's an enemy. Sometimes Mr. Krabs' cheap nature upsets SpongeBob when it causes Mr. Krabs to turn to devious ways to obtain money. Squidward and Mrs. Puff are both major enemies, they both hate SpongeBob, but he thinks they're his friends. Bubble Bass is a good choice too; the episode Pickles reveals that they had a past rivalry that still burns on now. Heck, somtimes even Patrick can be pretty nasty towards SpongeBob (his darkest moment is in Rule of Dumb). But Plankton and Bubble Bass are the only two characters that SpongeBob considers to be true enemies...
Ya, spongebob thinks plankton, mr. Krabs, squid ward, Patrick and mrs. Puff as his friends along every one he has every one he has met, but he does have a disliking for tonyfast jr. But he truly has dislikes bubble bass.
^Most of that is true. But SpongeBob doesn't exactly think of Plankton as a true friend, SpongeBob is just easily fooled by Plankton's plots as Plankton often takes advantage of SpongeBob's naive side. And good catch, SpongeBob is not so fond of Tony Fast Jr. after he got both of them injured.
Yeah, Patrick has had some antagonistic moments. His worst was in Rule of Dumb, after becoming the King of Bikini Bottom, Patrick did not just act mean, he actually became the exact opposite of what he usually is, which is actually pretty similar to Abrasive SpongeBob's case in The Abrasive Side.