Akihisa Yoshii has a unique relationship with every person he's close to, everyone in Class 2-F he was acquainted with in his first year of high school.
Yuuji Sakamoto is Akihisa's best friend, and frequently tricks him into doing something that ultimately screws Akihisa over. Yuuji is just about the opposite of Akihisa. He's calm, cool, and collective which usually leads to him giving advice to Akihisa (mostly jokingly) like a big brother would. Even though Yuuji is capable of testing into Class A, his nonchalant attitude caused him to test into Class F. Despite his academic capabilities, he's just as idiotic as Akihisa when it comes to certain fields, and they usually cause quite the ruckus together (but with good intentions).
Mizuki Himeji is one of many romantic admirers of Akihisa, arguably the main focus of his affections. The two of them were classmates in elementary school, the time when Akihisa gave Himeji her trademark Rabbit Hair clip. She cares deeply for him and is constantly trying to find a way to get his attention.
She loves him because he is always cheerful, sweet, and caring for others, but believes he only treats her so kindly because that's the way he is, not because he returns the feelings (but in actuality, Akihisa really does like Himeji, to the point where he let Himeji stay at his house because her parents attended a wedding at another country and couldn't return because their flight was delayed. Akihisa believes though, that she is in love with Yuuji).
Himeji is terrible at cooking. So bad in fact that her cooking is deadly to anyone who consumes it, even Hideyoshi, who in the manga describes himself as having a stomach of steel. This becomes a running gag, especially for Akihisa. Because of her affections towards him, Himeji always cooks up something for Akihisa to eat, usually resulting in his, and the rest of the boys, "deaths." Despite her sweet and shy personality, when the thought of Akihisa with another girl in any way enters her mind, Himeji goes into her "yandere" mode, and will do anything, no matter how crazy to punish Akihisa. Himeji also has an interest in getting photos of Akihisa, as shown when she asked Kouta for pictures of Akihisa in a sailor school uniform..
Minami Shimada is the "tsundere" of the show and has a deep interest in Akihisa. Though portrayed as hot-headed and harsh towards Akihisa (usually after he comments on her bust size) she only attacks him as a way of displaying her true feelings towards him, which can be seen when she forces him to let her call him "Aki" and gets him to call her by her given name. During the Shoukanjuu test run in the 2nd season, Minami's avatar apologizes for hurting Akihisa and asks him if he is okay, perhaps implying that Minami doesn't mean to actually harm Akihisa.
She's usually the first to "strike" to try and get Akihisa's attention and affection, but trips over her own steps, allowing Himeji to finally find her way to Akihisa as well. There are times during the 2nd season where Minami really begins to show her affections to Akihisa, which goes to show how much she really does care for him (there is even a flashback episode of the tale of why she loves Akihisa). In fact, Minami was Akihisa's first kiss something which shocked her as he was her first kiss. Like Himeji, she also has a large collection of photos of Akihisa cross-dressing, courtesy of Kouta.
However, just like Himeji, Minami cannot bear the thought of Akihisa being with another girl, and is swift to punish him in any way. Even if Akihisa treats Minami like a close pal, but as a guy, he really cares for Minami and the way he treats Minami is just different from Mizuki (Himeji). It is also hinted in some episodes that Akihisa likes Minami; he once mentions that she is someone he can be himself around. He even said that Minami has a charm to her and in the dub version he mentions that it's the guy part about her that he finds hot.
Hideyoshi Kinoshita is a very feminine looking boy in Class F with Akihisa and is considered the "trap" of the show. So much that people even believe he is more attractive than his twin sister, Yuko, much to Hideyoshi's dismay. Akihisa and Yuuji are probably the only two people in Fumizuki academy that recognize Hideyoshi as a boy, though Yuuji never comments on it, and Akihisa still has high hopes that Hideyoshi is actually a girl. A running gag in the show is for Hideyoshi to end up in girls' clothes, whether it be a maid's outfit or a nurse costume etc., and it causes Akihisa to catch nosebleed. Akihisa claims he is energized by just looking at Hideyoshi.
Because of his "beauty", black market photos of Hideyoshi are sold throughout the school for higher prices than any girl (or Akihisa). It is also a running gag that Akihisa is a VIP customer of the black market and is a frequent buyer of any photos of Hideyoshi that are in stock from Kouta. It was shown in an episode of the anime that Hideyoshi is his own gender, as he found it inappropriate to be in the girls' bath, while the boys and girls found it uncomfortable for Hideyoshi to change in the boys' bath.
Kouta Tsuchiya (known as Muttsurini in Japan) is the voyeur pervert of the show. His perverted ways and total attention on girls caused him to test into Class F with Akihisa. He keeps a camera with him at all times to snap photos of girls, Hideyoshi, and even sometimes Akihisa, and sell them on the black market to make some money. Akihisa is Kouta's VIP customer on the black market, always ready to buy the newest pictures of Hideyoshi and other girls. Because of this Akihisa is very quick to defend Kouta at any accusations people can make of him, and is very protective of Kouta's anemic condition (he nosebleeds at the slightest nuance of suggestive themes). Kouta is usually Akihisa's partner in crime when it comes to being a pervert and catching nosebleeds throughout the series.
Hazuki Shimada is Minami's younger sister. Because she's still a child, she is much more bold about her feelings for Akihisa than Minami or Mizuki, and she claims that she and Akihisa will be married someday. This, of course, puts Akihisa in generally awkward situations, mostly being put to trial by the FFF Inquisition which mostly ends up to Death Penalty, but he still treats Hazuki as if she were his little sister. Hazuki in the Japanese dub of the anime refers to Akihisa as "Baka Onii-Chan," meaning stupid big brother. Whereas in the English version she refers to him as "stupid Yoshii" or anything else referring to his idiocy, though Akihisa never seems to mind.
Akihisa is aware of her feelings for Yuuji and gleefully supports them like giving her VIP tickets to an amusement park for their date and set up a wedding experience for them, mostly to get Yuuji mad. The two seem to be good friends but whenever she is being nice to him she is also referring to Yuuji, like when she stood up for him and also Yuuji against the tokonatsu duo, she claims to have a soft spot for those "who are scared but still try" referring to both him and Yuuji.
Akira Yoshii is Akihisa's older sister, who has an incestuous desire for her younger brother. This is also used as a running gag in the show which makes Akihisa feel very uncomfortable. She's so daring as to even threaten to kiss him when he messes something up, and nearly succeeds on several occasions. Akihisa has no interest in her, but does care for her as a sister. She forbids him from having any sort of relationship with girls, though she allows him to have relationships with boys, much to Akihisa's dismay. She is the polar opposite of Akihisa, her academic ability is incredible whereas Akihisa's is terrible. But while Akihisa can cook, clean and take care of himself practically, Akira can't cook to save her life, and her housework abilities are horrible. It is also because of her horrible cooking that Akihisa found some immunity to Mizuki's cooking
Toshimitsu Kubo is the number 2 student in year 2 at Fumizuki Academy. Because of a misunderstanding, he's developed a crush on Akihisa, to the point where he acts like one of the girls and invades class F's classroom, though ALL of that flies over Akihisa's head and is used as a running gag. Kubo also panics whenever he has an interest in someone else other than Akihisa, as shown in the OVA series when Kubo becomes infatuated with a girl (unaware that it was Akihisa in a maid outfit), and ran when he saw Akihisa watching him about to purchase a photo of him as a maid from Kouta.
Miharu Shimizu is a lesbian in year two class D who likes Minami Shimada and focuses her attention on trying to get her to admit she likes her; she has an extreme hate for Akihisa whenever he does things with Minami, even if he has no intentions of doing anything, as shown in season 2 when Miharu believes that Akihisa "wants Minami's virginity", when he was intending on reaching the girl's shower room for other purposes.
In the light novels, Akihisa finally has an attacked from her when he wanted to run away from FFF Inquisition led by Yuuji. Because of her maniac attitude, Akihisa always had a hard time just like Minami when attacked by Miharu.