I think one of the things that I have found in my games is that the more enjoyable (non-villian) NPCs have unique voices. I don't just mean that the GM uses a different voice when they speak, (although I do think that is very important) but the character also have a distinctive personality that sets them apart from other characters (PCs and NPCs) in the game. Just because a character is a close friend to a PC, doesn't mean that they think exactly alike. The character should have at least a few traits that come out when they speak. When I speak in character for that character, I feel the character is a success if I don't have to tell the players what NPC just said that even if there is a roomful of them. For example, in my recent Changeling campaign the characters were dealing with several NPCs. One NPC was Samildanach, a werewolf who would spend most of his time in Wolf form. Having grown up as a wolf, he distrusted humans, was uncomfortable in human society and tended to speak in a growled voice. He was the grumpy one who was always wanting to "just get this over with." Another NPC that was along on their wild ride the last couple of adventures was Chase, a young Satyr stoner. He was lecherous as most Satyrs are, but the thing that put him apart from the Satyr PC already in our group was his enthusiasm and pure energy. He talked a mile a minute and constantly threw himself on poor Birch and later on poor Drusilla. He pledged his undying love for Drusilla That lasted about a whole adventure...until someone else caught his eye. While Denon was wallowing in drink and self-pity, while he was still pledging his love for Mera even as he started a relationship with Ling, Chase was....well....chasing a new fling and if his eternal love shot him down, there was always the next one.
Another thing I think is important for an NPC is that they have a real relatonship with a character, not just be there to supply them with quests, clues, etc. One of my favorite NPCs of all was Nall, a chimerical (dream) cat with wings. In my first Changeling game, a player created a dog-pooka named Buck. Buck was a gamer, through and through. He loved video games and roleplaying games. He also had a 3 point chimera that the player said "you can design." The first game he describes his character playing video games, trying to get his mind off of the weird reflection he saw in the mirror (he recently discovered his Fae self by finding a dog-face looking back at him in the mirror). I decide that now is the time to spring his familiar on him. being that his character is into video games and anime, I think of something I saw in a video game recently, a flying cat. A flying cat come bursting through his window to land on his bed. "Hey Buck, how's it going?" He chases the cat around the room until he tires out from chasing it. "How do you know my name!?" The two bicker and fight for most of the campaign. Nall seems to be around only to insult and harass Buck but on several times he pulls Buck's butt out of the proverbial fire. Then near the end of the game, Nall disappears for sometime. When Nall returns, Buck tries not to show how much he missed him but the two are both obviously happy to be reunited. The PCs go off and save the world, but in the process Buck sacrifices his dreaming self. The final scene of the final game has the PCs visiting the human Buck in an insane asylum. Buck is heavily drugged and watching tv in the common room. A winged cat is sadly curled up on his head waiting for him to remember his true nature. I think what made Nall so successful is how much of a relationship he had with the PC. Ideally, every character should build bonds like that. It really gives the game some depth.