Short answer: D&D without the sacred cows isn't D&D.
Long version: Very few of the things in D&D truly are "sacred cows."
So, the question is, what are the sacred cows? Offhand, I'd go with only the following:
- d20 for task resolution
- dice rolls for damage
- hit points for tracking damage
- saving throws for avoiding "bad stuff"
- 6 ability scores (Str, Dex, Con, Int, Wis, Cha)
- Classes & Levels that determine combat effectiveness and other special abilities.
- humans, dwarves, halflings and elves as core races (there may be others, but these 4 will always be there)
That's it. I don't think specific classes, arcane/divine magic, spell slots, AC, or anything else is a true "sacred cow." While the concept of "Saving Throws" is, the specific ones are not. The skill and feat systems certainly aren't. IMO, D&D will never have skill-based attack bonuses, or do away with hit points, dump the d20, or go classless or level-less. It just wouldn't BE D&D.
I could see Defense replacing AC, armor as DR, a different magic system, different classes, revisions to the skill or feat system, et cetera. I imagine there will always be some form of "magic-user" class, a "fighting man" class, and a "thief-like" class. I imagine BAB will stay and stay a class feature, as it's a very elegant way of handling "to hit" rolls.
Beyond that, I wouldn't dare speculate.
And as long as it held the above cows, I'd still play it. Which is why I still think of my Iron Heroes games as "D&D." It shares all those cows.