1. Jonathan Joestar, A Short-Lived Gentleman (JoJo's Bizarre Adventure)
Calling out any one character as particularly strange in a show with "bizarre" right in the title is a bit tricky. JoJo's Bizarre Adventure doesn't always stop to make sense in its multi-generational epic. Meanwhile, just about every character -- hero, villain, or supporting cast -- stands out to some degree.
The difference between Jonathan and the rest of them is a point of comparison. We know what decades of Joestar men and women seem and act like. Not a one of them matches the personality of the original protagonist that kicks off the series.
Born in the 1800s, the first JoJo begins life looking like a "true gentleman." He's kind, caring, relatively well-mannered, and comes just shy of naive at times. All of which are traits that work against him when one Dio Brando enters his life -- an adoptive brother who is pretty much none of those things.
Dio wastes no time in turning JoJo's life upside down. The newfound sibling turns his friends and father against him, and wouldn't you know it just happens to become a vampire at the most inconvenient time. Just when the world was starting to come back to Jonathan's side.
Even then, through hard work and determination JoJo learns the secrets of Ripple, a.k.a. Hamon, energy. This turns Jonathan's untapped wellspring of enthusiasm (and, y'know, his fists) into a weapon against his monstrous would-be brother. Though in the end it's not actually enough to keep him from a very untimely death via a pair of neck tentacles. This is still anime, after all.
Compare this to following generations of JoJo's. Characters like Jonathan's grandson Joseph are anything but gentle. Every JoJo that follows has the capacity for a mean streak, as well as zero interest in honor or playing fair -- wisely opting to cheat or flee when the situation calls for it. Ironically, this is exactly what makes the rest of the Joestar clan stand out from the mountain of martial arts anime do-gooders. Making Jonathan, by virtue of being the most mundane hero in the series, a bit of an oddball.
2. Maes Hughes, Happily Realistic (Fullmetal Alchemist)
We've danced around including this character on one of these lists for a while now. A long while indeed. Now the time has finally come for Maes Hughes to get his dues.
In a sea of often heartbroken, single-minded idealists Maes Hughes is a goofy ray of sunshine. At least on the outside. While just about every other character in Fullmetal Alchemist has a bound-and-determined purpose that drives their every action, Hughes... is a bit of a slacker. One who constantly talks about shirking his duties to spend time with friends, and especially family.
The latter subject is one that comes up ad nauseum throughout the series. Hughes is nothing if not a family man. Certainly by the time series stars Ed and Al Elric come on the scene. In fact, the intelligence officer won't shut the hell up about his wife Gracia, and three-year-old daughter Elicia, even when the often very tragic fiction of Fullmetal Alchemist is at its highest points.
Which isn't to say Maes Hughes is ineffectual. It's just the opposite, in fact, which is yet another reason the character is on this list. As it turns out Hughes is incredibly pragmatic -- often noticing and accepting hard truths before anyone else. A trait which is likely the result of many not-so-pleasant years in the military. So when it comes time to, say, investigate a dead body -- or make one himself -- he does what's necessary without much fanfare.
Unlike nearly every other character in the franchise Hughes doesn't let this consume him. Rather than sink into melodrama he throws himself into the good parts of life. Compared to his terse and idealistic bestie Roy Mustang, or the aforementioned Elric brothers, this makes him a rather three-dimensional supporting character.
Sadly, it's these traits that lead to his eventual death.
Whether in the manga, the 2003 anime, or its 2009 redux it all ends more-or-less the same. With Hughes learning the truth that his country is under control by the semi-human homunculi. Envy, the group's resident shapeshifter, uses his wife's image to get in close and snuff out this ray of happiness in a bleak world. Though thankfully the murder propels the rest of the cast to eventually learn the truth for themselves.