Your guess is as good as ours, but...
Grim Fandango (and I think EMI too) had joystick support showing that they are indeed fitting the technology for cross-platform games, but I feel that there is a reason they have left mouse support out in the past... Really too hard to steer a character with the mouse without pont-n-click. As action-oriented as FT2 is made out to be, I think they may be bringing the mouse back, and adventure gamers will have to adapt to FPS settings to use it.
For instance: In Jedi Knight II: Jedi Outcast, I set my right mouse button as my "move forward", my left mouse button for firing, my wheel to cycle through weapons, and my keyboard for jumping, crouching, force powers, etc.
Now, let's say that FT2 uses the same idea of being able to use mouse and keyboard for what you want to do - since it's an action-adventure and not a "pick the best insult" kind of dueling, players are gonna be geared for action at all times. So they could set their mouse and keyboard similarly: right mouse as move, left as use/attack (depending on the situation) mousewheel to cycle through both weapon and non-weapon inventory, and keyboard for everything else.
This, of course, is just a guess.
As far as Mark making a return, I highly doubt it. At least in the Ripburger role. Granted, my uncompleted fanfiction "Trail of Fire" has Ripburger basicly crushed in the fall at the end of Full Throttle, but rescued and revivied by the Cavefish (this segment of the plot involves the cavefish hijacking trucks to keep stocked in drug ingrediants for a medicine which saves their lives, but makes them ultra sensative to the sun...) and he becomes the new Cavefish leader, but I highly doubt LucasArts would do something similar.
Too many fans cheered when Ripburger tested gravity that one final time. It's a big world out there, friend, and the Polecats are a roving gang tied down to nowhere. While the trailer does show the gas tower and (possibly) the Kickstand, it also shows a sign for El Nada --- If Mark returns, he'll most likely be someone else.
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* The "works" is a beating so intense, you'll pray for death.