One of the very interesting things about the evolution of D&D over the years is the attitude about pc failure.
In the early years (and I'd say up through much of 1e), it was a given in many groups that pc survival rate was low- that, say, half of all pcs would die before attaining 2nd level.
In late 1e (especially DragonLance) and then 2e, the emphasis on "story" started a tendency towards plot immunity for pcs that seems implicitly stronger than ever in 4e (with a mix of attitudes in 3e). For example, at the end of Keep on the Shadowfell is a section on "Failure" that basically says, "If the pcs fail, let them go pretty much without consequence".
How do you feel about the chance of pc failure? There's a great range of opinion on this, and I think DnDN will support a wide array of playstyles, but what's your preference? If you, as a dm, use a "world will end" plot in your campaign, are you prepared to end the world if you have a tpk? Do you prefer a "no pc dies without the player's permission" style? Do you like a game where pc turnover is common or rare? Do you like it when there is a real chance of actual mission failure, and real consequences, or is it more fun when the pcs always win?
As a DM, I am prepared to follow through on any consequence or evolution of a situation that has been placed inside the game world. I wouldn't place it otherwise.
As for player permission, the players grant permission for their characters to die when the game system is chosen and they agree to play. Some games line Teenagers from Outer Space they system prevents death. For other games like Hero emulating 4-colour comics, death is both rare and need not be "real" -- characters come back all the frikking time. For other games death is common and final.
As for PC turnover, it depends strongly on the game system in play -- specifically the ease at creating and integrating a new character. For early D&D, fast turnover was fine. For Hero, Ars Magica, 3.X not so fine.