I'm wondering if doublequestionmark's question is which actor will be hardest to replace because we closely identify their performance with the character or which role is so challenging that only actors at the top of their game can rise up to the occasion and play the roles?
If you view Jesus as a mythic figure, he's a martyr and a saint and not really all that interesting. I don't think the role is especially hard to play. Singing it on the other hand...
As for the role of Hamlet, at this point there has been so much written about Hamlet and so many examples of how to play the character that most actors who approach the role probably have their work cut out for them.
The challenge is less to fulfill expectations as it is to find new ways to break the mold (Bernadette Peters in Gypsy and Patti LuPone in Sweeney). So a role like Elphaba or Frankie Vallie don't really fit because they are specifically designed parts that have to be played a certain way, much the same as Belle from Beauty and the Beast. While a few years may give perspective on some of these roles (although probably not Frankie Vallie) while we are speaking right now, audiences go to see Elphaba played the way Idina Menzel did it. Wickedians can fuss over who does the melisma differently but Shoshana Vs. Idina is DEFINITELY not Angie vs. Patti.
It's such a loaded question anyway. Are you saying shoes to fill in terms of the demands of the part? The excellence of the previous actor? Who will sell more tickets? etc.
yr ronin,
joey