S.T.A.L.K.E.R.: Clear Sky will be a prequel to the events that occurred in Shadow of Chernobyl. This time, instead of playing as the Stalker Strelok, you will be in the role of a Mercenary called Scar. Your character is shown to be immune to the effects of the zone. The game will also focus more on the different factions of the zone and them fighting for control of land area. You will also be able to join 5 of those factions(Duty, Freedom, Bandits, Mercenary, and the new factions, Clear Sky).
Clear sky is due out this August 29thfor real this time!

Here's the info that we know for sure so far:

-The player assumes the role of a mercenary called Scar whose goal is to kill the Stalker Strelok. It is confirmed that you can't kill Strelok, as this would contradict later events in Shadow of Chernobyl. But the player will be able to see him in the game, and the storyline is directly tied to him.

-The game is still set in the Zone, so around half of the game's locations will have already featured in Shadow of Chernobyl (The Chernobyl Nuclear Power Plant, the Agroprom Research Institute, and the Red Forest are confirmed locales). The entire gaming Zone will consist of 50% completely new areas, and 50% twisted, pre-Shadow of Chernobyl versions of old areas, as well as some removed ones. One of the new locations is the Swamp, which will be large.

-There will be more anomalous activity than in the previous game (with new and more varied anomalies). The anomalies, artifacts, and their detectors will be greatly varied. For example, the detector will be a device that is held in one hand, while the other holds a small firearm, like a handgun. Long-barreled weapons such as rifles cannot be held at the same time as the detector. New mutants have been added, and old ones have been enhanced. Blowouts are going to be included(finally).

-The AI will be able to throw grenades. When the NPCs throw grenades, a yellow icon appears on your HUD, warning you. The developers decided to do this after a lot of people had trouble avoiding grenades.

-Beside the use of grenades, NPCs have become much more intelligent; they coordinate and work very well in groups, interact in groups, and with the player. At the Igromir gameshow, no one (including the developers) was able to kill more than two of four bandits armed with AKS-74Us and Sawn-Off Shotguns before dying.

-The AI now have day and night routines. Since smart terrain for the AI has been expanded, now the world can be physically interacted with.

-The engine has had a mass of modifications, almost to the point of being completely overhauled. The lighting has been almost completely overhauled (e.g. the nights will be darker and there is completely dynamic lighting, all light sources can be altered, shot, or diverted), and volumetric light has been added. The engine will support DX8, DX9 and DX10, keeping system requirements similar to the original. This cannot be confirmed until the game is shipped, however. The variety of animations has been greatly expanded. Enemies can blind-fire now and use cover in more ways than in Shadow of Chernobyl. The game will have more realistic looking weapons and more detailed player models and water effects. Your view focuses on your weapon when reloading, the background becomes blurred. Certain parts of the landscape will be destructible. There will be more dynamic objects.

-The developers are considering adding vehicles into multiplayer.

-One new mutant has been confirmed, the "Marsh Bloodsucker", who will be invisible. This bloodsucker was seen in the swamplands level, and has the ability to grab NPCs and the protagonist and throw them high into the air, before taking them back into the swamps to eat.

-The game will be available for both retail and digital download, but the digital download will be exclusively from Steam.

-This game will require the same system requirements as the previous game (S.T.A.L.K.E.R Shadow of Chernobyl)

-Can now repair your weapons and armor and as a bonus you can now upgrade them and fine tune them to be more personal and more reliable.

-Fast travel is to be added to allow easier travel between areas. You can pay an experienced Stalker, like Guide from Shadow of Chernobyl to lead you through a short, but very dangerous path full of hazards from one area to another, in order to avoid having to run through the entire level.(And miss all the nice mutants!?! For shame!)

-And heres a big one, we can now kill those pesky crows that fly around without having to use a mod now.

Videos
E3 07 gameplay Vid
Marsh Blood Sucker in action
Games opening FMV
E3 08 Footage
Developer Walkthrough of Marsh Level
DX10 video demo
E3 07 war video

Sources:
Wikia
Official Forums
OBLIVION-LOST

If I missed anything, feel free to add more.