Alternating between 4-Koma and the normal... non-4-Koma format, Hozuki-san Chi no Aneki is about a brother, Gorou, who lives with his sister, Haru, (Not related by blood; step siblings?), and has a sister complex. A huge sister complex. BIG. It's what drives most of the jokes, concerning him at least, and how the sister trolls him about it; with him ending up in compromising positions infront of his classmates and peers; him trying to prove his worth and manliness, the usual stuff. It has the requirements for a comedy about a brother/sister duo and it works. The short volume series does work in it's favor as it doesn't overstay it's welcome but on the other hand, those left wanting for more (Me), are only left with what little there is.
Aside from the comedy, it tackles drama and friendship, more prominent in the latter half of the series. It does it well and even makes it twistedly comedic in it's glory while maintaining an aura of seriousness. Dramedy, if you will. More often than not, it's whenever it's in the regular format so if it changes, you know some serious things will be going down. Relatively serious at least.
The side characters add to it by revolving around one or both of the mains. Be they siblings, friends, stalkers, saviors, take your pick. As the more often seen style of 4-Koma declares, they aren't meant to be deep, excluding the mains. They, on the other hand, have more depth than one would suspect and, once again, in it's favor.
The sum of it's parts are comedy first and foremost, with a brother complex as the brunt of most of the jokes, perversion as a high secondary, and serious drama a somewhat distant last. It may get tiring to those who might not like jokes revolving around the same topic but that topic is the main plot point; what the manga revolves around. But then again, it's a 4-Koma and from my initial belief and inexperience with them, that's how a good number of them should be.* It was fun while it lasted, and a worthwhile read while it lasts.