Once again, I end up looking at Kodansha properties, even though Del Rey is not exactly rushing to license new things, Dark Horse seems mostly interested in reissues, and pure long-running shonen is not quite Vertical's thing. I guess until Kodansha USA gets its act together, this will just be pure hypotheticals.
Looking at currently running series in Kodansha's flagship Weekly Shonen Magazine, there isn't much that's actively licensed right now. Negima, Air Gear (which is already in 'omnibus' format), Zetsubou-sensei, Fairy Tail, and Code: Breaker. 5 series out of about 30 that Wikipedia notes are still running at the moment in the magazine. Kindaichi Case Files was once licensed by TP, but was pulled when the Kodansha titles vanished, and was likely already canceled due to low sales even before that.
We can also leave out Hajime no Ippo (a 90+ volume boxing manga) and Godhand Teru (a 50+ volume medical drama) as being far too long to seriously recommend, and of course we can leave out all sports manga. For Magazine that's pretty rough, as it culls Ahiru no Sora, Ace of Diamond, Shinyaku "Kyojin no Hoshi" Hanagata and Area no Kishi, all best-selling titles in Japan that won't see the light of day here unless Cross Game somehow turns everyone's heads. Lastly, I'm leaving out 4-koma and gag manga, so no sign of Mou, Shimasen Kara or Seitokai Yakuindomo.
(I'd personally love to see SYD over here, but that's also unlicensable for another reason - it's utterly filthy.)
Cut all those back, and also eliminating series too new to really be considered, and you're left with precisely one title that's unlicensed yet has potential. It's called Yankee-kun to Megane-chan, and has been running in the magazine since 2006. It's at 19+ volumes and still running, which is considerable but not so large as to be unprofitable. It has two very strong lead characters. It's also very funny. It has a live-action series that ran in Japan earlier this year. And it's been a big success in Singapore, where it's called Flunk Punk Rumble.
What's holding it back? Well, first off it doesn't have an anime. Live-action series are all very well and good, but far less marketable to the West than a nice anime tie-in. Secondly, it features that dreaded word that sends publishers screaming to the hills: delinquents. Not quite on the level of your typical Young King title, and at least they try to keep the cast vaguely attractive-looking, but teen gang titles haven't really been seen here since Tokyopop had to let go of Shonan Jun'ai Gumi and GTO.
Lastly, and perhaps most importantly, it has zero elements of fantasy. The boy is not a vampire, the girl is not a ninja. These are high school students, getting into high school comedy. Even School Rumble, the title's closest equivalent, played around with girls who could read minds and men who could talk to animals.
The premise, which I suppose I should mention at some point, is that Daichi, our hero, is trying to slouch through his high school life as a typical Yankee (a Japanese term broadly used as delinquent). Sadly, the class rep, Hana, has taken notice of him, and is making it her job to force him to shape up. Of course, as he quickly finds out, she has more than just personal interest in him at stake here, as she is highly influenced by her own past. Could this glasses-wearing annoying girl have really been one of the most terrifying delinquents in all of middle-school?
Besides School Rumble, there's a lot of GTO to this, in that much of it is teaching gang-loving apathetic Japanese kids that there's a more productive way of doing things. I happen to be a big fan of that sort of thing, another common Japanese trope. Could this appeal to Western readers? I think so, given the right push. It has a likeable cast, a lot of good comedy and fights, and some mild romance between the leads.