I think certain characters will benefit from the recognition that they work best within a certain mileau.  Those who have been around for decades as pointed out, will likely be hurt the most through cross contamination with other genres.  I love Batman as a figure inspired by the pulps; a colorful daytime crusader; an avuncular alien fighting good guy; mysterious creature of the shadows; but things started heading south for the guy after his first half century.  Still, he had a pretty good run before then especially given how cavalier a lot of writers were with where the character got to go.

Professor Hugo Strange

md62's review of Detective Comics 469-479 covered the return of Strange after an absence of some 37 years from the texts.  I guess it's easy to have a pretty good score card when you get to take such lengthy breaks, but I've been impressed with this character's performances whenever they occur.  Here's a guy who has probably appeared in about 10 storylines since 1940 and yet almost everyone of those tales is recalled as a classic.  Those early Golden Age tales with Batman up against his Man Monster creations typify the era readers applauded later writers for going back to.  The Englehart/Rogers 'Strange Apparitions' run has been celebrated since it ended and Hugo was the link which ran through it. 

Doug Moench's Prey is often cited as the best storyline Legends of the Dark Knight had during it's 200 issue or so run. 

Moench would also utilize the character in the 1986 Batman Annual which featured the most original method I've ever seen of handling a super villain whose discovered your identity.  Simply tell the police that "yes, this enemy of mine did learn who I am so I hypnotized him into thinking I was someone else - in this case, my friend Bruce Wayne".

Alan Brennert is the best unknown Batman writer there has ever been (author of 'To Kill a Legend') and his little known masterpiece Interlude on Earth 2 utilizes Strange as a physically broken old man whose unique motivation in this issue of Brave and the Bold 182 was 'suicide by superhero'. 

Though I'm no fan of what the main titles did with Batman during the period, I found Devin Grayson's four issue Gotham Knights storyline to be the exception to the rule and yes, you guessed it, it featured the return of Hugo Strange after an absence of 10 years. 

I know it's not well known and it might just seem that at this point, I'm simply equating 'Any comic with Hugo Strange in it' with 'MASTERPIECE' and... well, actually yeah, I sort of am.  Knowing that Hugo Strange is on the verge of confirming his true identity, Bruce Wayne takes the extraordinary measure of using self-hypnosis to forget that he has anything to do with Batman and truly becomes the simpering, useless playboy he had previously only pretended to be.  It's one of those plans where for it to work, he can't confide in anyone who Strange might be observing.  He just has to count on Dick Grayson unwittingly giving the secret code at the appropriate time and hope that the message the code is hidden in means enough to him to recite it when all looks lost.  In other words, it's one of those stories where Batman loses everything before claiming victory.  Not sure if I did it justice, but I do know that when Grant Morrison used the same idea during his later run, he was lauded as a brilliant visionary.

Not to say that Hugo Strange has a perfect score card - Moench's sequel to Prey was a great disappointment - but if you ever wanted to create your own collection of Greatest Batman Stories Ever Told, you could play it safe by simply tracking down every appearance of this friendly fellow.