For my own reference and perhaps others' interest, this entry is to keep track of Simon/Will's friendships/relationships.
[This list is incomplete and ever-expanding. Last updated 10/13/10.]
SPECIAL
enchainement (River Tam, Firefly/Serenity) - Formerly known as Serenity. Simon's sister, his heart and the most important thing in his life. Before her arrival in Edensphere, he wanted desperately to either find her in the Sphere or find some way to go back home to be with her, even though his current knowledge of their situation is limited and thus he still can't really say WHY he wanted to. Through the memories he and Inara have received, Simon has pieced together that the two were on the run from something, that they came to the ship Serenity so that Simon could hide her, and that River has nightmares about something that was done to her at an academy; anything further than that still eludes him. Finally, in November 2009, familiar handwriting whose origin he couldn't quite place appeared in the journals, and a chance meeting in temporary housing made the connection fall into place- it was his sister. She disappeared briefly at the end of February 2010, completely crushing Simon. However, she reappeared about a week later, with her memories erased again and now calling herself Qǐ. She immediately latched onto him again and seems scared to leave him.
She often describes their relationship as "the moon and the planet", with Simon as the moon. He believes this to be a fitting description, as his life tends to revolve around her as he tries to help her conquer her demons and remain as grounded and sane as possible.
galacticgeisha (Inara Serra, Firefly/Serenity)- Formerly known as Companion. Inara and Simon came from the same place and have seen and/or heard each other in some of the memories they have received. He cares very deeply for her and trusts her implicitly, especially because he feels like she is one of the few people who truly understands his intense devotion to his sister, and thus often comes to Inara for advice and comfort whenever the Sphere decides to mess with him.
floating_bamboo (Ukitake Jyuushiro, Bleach)- Koi is Simon, Qǐ and Fracta's housemate, and pings Simon strongly for Shepherd Book, both in a "badass old man" way and in a "this is someone who will take care of me and my sister" way. He's taken to calling Koi "Dad" or "bàba" (Mandarin for dad/pops) as a sign of respect for the role he plays in his life. He is also glad to be living with Koi, as the man is very sickly and has on occasion needed emergency medical attention.
ice_echani (Brianna, Star Wars: Knights of the Old Republic II) - Though it seems like a rather unusual friendship due to their quite opposite natures, Handmaiden is considered a very close friend by Simon and is someone whom he trusts completely. She wished to teach him how to fight in spite of the fact that he is a better healer than warrior and has been giving him self-defense lessons. They have also developed a connection on a deep level because they both understand the pain of missing someone they deeply loved from their past.
snowburned (Kuchiki Rukia, Bleach)- Kazahana was one of the first people Simon got to know due to the fact that they are both medics and thus work together a lot. He generally feels comfortable sharing things with her and at one point developed romantic feelings for her. However, he never found an opporunity to tell her so, and when Kazahana began to date Kiba and Simon came to the realization that romance could likely not work for him as long as his sister was his first priority, he silently let go of them.
POSITIVE
pinkhairedchild (Kusajishi Yachiru, Bleach) - Blood sometimes confounds and disturbs Simon simply due to her personality and the fact that she is a small child who works as a Guard and totes a sword around, but he is finding himself drawn to her ability to see the bright side in almost anything.".
seeya_next_life (Axel, Kingdom Hearts) - Though not well-acquainted yet, Lea's a very pleasant person and seems to genuinely care about his siblings, making him a good guy in Simon's book.
weaver_girl (Inoue Orihime, Bleach) - Lea's twin and a kind, caring young woman who always does her best to look out for others. The two have started to become closer due to the fact that Kagerou believes she is Koi's daughter, and he is slowly beginning to consider her to be another sister.
felinemystique (Shihouin Yoruichi, Bleach) - Simon and Bastet are not well-acquainted, but she pings him for Zoe, and so he feels as though he is safe with her as Guard Captain.
wayofflowers (Retsu Unohana, Bleach) - Bellflower is another medic, who has a slightly-aloof but still caring presence. Simon gets along with her very well, especially because she and Koi came from the same world.
spandexisyouth (Maito Gai, Naruto) - Youth's relentless enthusiasm, drive to help other people, and desire to gain knowledge, even in the face of potential difficulties and dangers, is something Simon finds very admirable and appealing.
redhead_rabbit (Lavi, D. Gray-man) - Another fellow medic. While not as close to him as some others, Simon still enjoys Rabbit's company and considers him a good friend.
mythgravenblade (Cecil Harvey, Final Fantasy 4) - Paladin is gentle and was extremely helpful in healing the injured after the Sphere Fire in October 2009. Simon wants to get to know him better as he feels they would get along well.
darcyredux (Yoshiya "Joshua" Kiryu, The World Ends With You) - During the fire, Simon treated Composer for injures and smoke inhalation; as a result, Composer feels in his debt, and Simon is happy to mentor the young man as a helper at Medical. Since Simon forgot the fire when he died in May 2010, however, he also forgot Composer's reason for looking up to him.
NEUTRAL
blue_shields (Schuyler "Sky" Tate, Power Rangers S.P.D.) - Simon and Sky have a passing acquaintance with one another due to their mutual relationships with Ghost and Inara. Simon is sometimes secretly baffled as to what Inara sees in Sky, as he sees the man as very cold, rigid and unfriendly. (Sky, for his part, is put off by what he sees as Simon's unhealthy obsession with his sister.)
fugue_angel (original character) - Simon met Fugue in person when the mysterious man was searching for the library- and inadverdently gained access to the place himself when he followed Fugue and Ghost there. Simon has no reason to dislike Fugue, but no particular reason to like or trust him, either, especially since others seem to be highly suspicious of him.
flenceburgsbest (Lezard Valeth, Valkyrie Profile) - Lezard is Head Medic and thus someone whom Simon must defer to and take orders from. However, there's something about the man that deeply unsettles him, and so he tries to avoid him where possible.
man_genius (Topher Brink, Dollhouse) - Simon and Genius are co-workers, and Simon is frankly astounded and puzzled by the fact that his sister has latched onto Genius. He does not trust the other man at all nor particularly like him, but tries to get along with him for Qi's sake.
NEGATIVE
None so far
GONE BUT NOT FORGOTTEN
gundrifter (Vash the Stampede, Trigun) - Geranium and Simon were born together and had a relationship as close as any pair of biological brothers. The two trusted each other completely, and shared the deepest secrets from their pasts with one another. Geranium disappeared in January 2010, which completely devastated Simon. He wears his brother's signature red coat in remembrance of him, and also keeps his journal, salvaged from the library.
localdisaster (Vash the Stampede, Trigun Maximum) - Broom was the second incarnation of Simon's twin, Geranium. Simon was crushed when he saw his brother's handwriting appear again and realized that he'd forgotten the Sphere; he tried to reforge their relationship, but did not have much time to before Broom disappeared.
droppedastitch (Sally, The Nightmare Before Christmas) - Doll and Simon found each other to be confounding, as he found the idea of creating a ragdoll like her to be rather repulsive and she did not understand why, but they still got along very well.
esp_optimism (Maya Fey, Phoenix Wright) - Simon found Medium to be a helpful person and enjoyed her sunny disposition.
catwouldbeking (Sho Minamimoto, The World Ends With You) - Tybalt was somewhat odd to Simon, but he also found him to be extremely intelligent and overall good company.
kochsnow_flake (Winifred "Fred" Burkle, Angel) - Fracta was one of Qǐ's closest friends and one of Simon's housemates, whom he took in after his sister befriended her. He recognizes that Fracta is broken in a similar manner to Qǐ, and loved her as a second sister.
redrobinhood (Jack Landors, Power Rangers S.P.D.) - Simon and Ghost developed some sort of connection due to the fact that they were both led to the library by Fugue and thus know at least some intimate knowledge about the Sphere. He was also one of the few who knows that Ghost did not in fact get killed when he vanished for several weeks in the summer of 2009, as he was treating the wound the tree caused after his return.
sixthsinner (Nicholas D. Wolfwood, Trigun) - Previously known as Chapel. Simon found Nicholas to be a pleasant enough person and allowed him to stay in his house when Nicholas's own was destroyed in the fire. Slight ping for Shepherd Book, what with the whole wandering-preacher thing.