I don't really like Natsuno's personality, but he is an interesting character to watch. Seishin and Toshio /are/ too old, but they're drawn pretty young! True, most of their chapters involve introspection that can't very well be translated into an anime/manga, especially a shounen one. Ozaki is more action than Seishin, and it would be impossible to cut out the medical part of the story entirely, so I think that's why he has a biiit more screentime than Seishin. Natsuno really pushes things forward, like by aggravating Megumi here. So then the focus is Natsuno, then Toshio, then Seishin; but even if they cut the last two out a little, they still become really memorable characters in the anime! Or else they wouldn't have so many fans.

It does look like Seishin's the central character of the work, if only because he's the one that undergoes the most change throughout. At first, he's a meek, depressed monk that doesn't really know what he's doing, but several months later, he's a werewolf priest that proactively kills Ohkawa! And it seems that he's finally found what he was looking for. I'd even say that Shiki is also a story of how friends come and go; Seishin starts off as having Ozaki as a best friend, and the 'infectious disease' is a catalyst towards them realizing how decreasingly compatible they are. As Toshio starts to understand Seishin less and less, Sunako starts understanding him MORE, becoming his new best friend. In the end I think Ozaki and Seishin still think fondly of each other not because they still like each other's personalities but because they have memories of themselves liking the other's personality, and that kind of thing is hard to let go of.