My sacred cows that I'd like to see slaughtered, chopped into hamburger, and served up grilled with a slice of tomato, a bit of lettuce and some mayo are:
* d4 Hit Die for wizards (or for anyone - it works great in OD&D, but the scale is all wrong now - make d6 the minimum for Hit Dice)
* Magic Missile (get rid of it, make the wizard roll for an attack and have it do more damage, but no autohit spells)
* Spells per day (e.g. Vancian Magic - I don't care if there are some spells a wizard has to prepare and use on a "per day" basis, but every spellcaster should have his array of offensive and defensive spells that are usable at will or some number of times per encounter. A fighter doesn't go into combat without his sword and a wizard shouldn't ever be left without something to throw at an enemy).
* Invisibility that goes away after making an attack (I've never liked this rule - move invisibility to a higher level effect and drop the arbitrary duration constraint)
* Saving Throws (make everything consistent with the d20 attack/defense mechanic. There really shouldn't be any difference between a "touch AC" and a "Reflex save" - they both measure your ability to get out of the way of someone trying to hit you. So roll them together into a static number and let the person doing the acting do the rolling consistently in every case.)
Things that D&D needs to still be "D&D" to me:
* Classes
* Races
* Levels
* Rules that support a game centered around going underground, killing monsters, and taking their stuff
* Rules that don't get in the way of doing things other than "going underground, killing monsters, and taking their stuff" if you want to do more than that
* Hit Points
* Compare a d20 roll to an opponent's Armor Class to see if you hit
* Dragons
* Dungeons
Not to say that I don't enjoy games that don't have those elements - because I do. But any new edition of D&D needs those things for me to say "that's D&D". If I can't talk about how my 10th level Dwarven Fighter explored the Caverns of the Insane Warlock and got a lucky 20 to do the final X points of damage needed to smack down a red dragon and take his stuff, I'm not talking D&D. I may be talking a game that's a lot of fun on its own terms, but I'm not talking D&D.
(And note that I'm not saying that EVERY D&D game has to be like that - just that the game should support that kind of play. If I want to play a Planescape game where my 6th level Tiefling Spellthief beats a rogue Arcanoloth sage in a riddle game, that's still going to be D&D as long as the game also supports the play style above).