What I've read:
Alan Alda will portray
a Republican candidate (and the eventual nominee) in the upcoming Presidential election to pick Bartlet's successor.
Jimmy Smits will portray
a former mayor of Houston (woo hoo!) who becomes a Democratic Presidential contender (and the eventual nominee, I believe).
As for Leo:
He is not dead. After his recovery he returns to the Bartlet administration as a senior advisor.
is promoted to Chief of Staff.
resigns. OK, we've seen this on NBC's promos. Not known is the reason for the resignation, although it's likely a reaction to C.J.'s being promoted to CoS over him. Not sure if the actor is leaving the show or not.
, like Toby, is upset at being passed over for C.J. and leaves the staff to run the Presidential campaign for Smits' character.
leaves the staff as well, and goes to work for Will on Veep Bingo Bob's campaign. Since Donna no longer works for Josh, they finally begin a relationship.
serves out his term. It's possible that this is Martin Sheen's final year. If he re-ups, they'll stretch the campaign out through the first part of next season. If he decides to leave, they'll speed things up and he'll ride off into the sunset at the end of this year.
Former V.P. Hoynes returns, but what role he plays is unknown.
My guess as to the eventual direction of the show:
Well, Presidents are limited to two terms, and since the show began in the middle of Bartlet's first term you had to know this cast would only go 6 years or so. This is the transition year. I think TWW will be reborn next year (perhaps as late as mid-season) with a Republican President (Alda) and a completely new cast.