#1: How will resource management work? I'm extremely skeptical of the per encounter mechanic. I don't care for it in ToB and I can't see it being particularly appropriate to combat maneuvers and it's only marginally better for magic. I've seen the seeds of good ideas (mostly from other ENWorlders, not WotC), so I remain open to seeing what they come up with.
#2: The Ranger Actually, I've pretty well written this one off. The ranger is a warrior with an strong survivalist/outdoorsy bent. He isn't a rogue that's good in the woods. He isn't a slightly more physical, less magical druid. The ranger archetype, IMO, has more in common with the barbarian than with the rogue, and they aren't much closer to a druid than to a sorcerer. At this point, though, I think the definition of what "ranger" means is so diluted with all the different editions that it's a meaningless word. I'm hoping that WotC drops the term and calls the 4E ranger a "scout".
#3: Will this still be "D&D"? 25+ levels of spells. Spell adder items. Martial abilities similar to spells. Power sources. Combat roles. Per encounter abilities. Three hit dice at first level. That's a lot of change. All I want is a system that lets me play the kinds of games I played with 1E, just more smoothly, easier, and higher definition (i.e. rogues have skills rather than set abilities, multiclassing works better, swashbucklers are workable, etc.). I don't want Exalted, Earthdawn, Legend of the Five Rings, or any other fantasy game.
#4: Ease of play WotC says they are working on reducing prep time and in-game delays caused by complex and/or idiosyncratic rules. I hope this is true. I don't have the time I used to.