I've GMed a lot of, and played a bit of, high level FRPGing - AD&D, Rolemaster, 4e D&D.
4e D&D worked well, and to me it seemed pretty well designed. There is a fairly clear progression of effects, eg from slow or prone on Heroic tier encounter powers to Dominate on an upper Epic tier encounter power. Epic destinies establish a clear logic and place in the world for high level PCs.
The high level NPCs and creatures in the MMs were a bit underdone, at least for my group, but I didn't find it overly much work to build variants that had a bit more condition removal/avoidance (using creatures like the MV dragons, and hydras, as inspiration) but didn't simply shut down the players' successful abilities.
I did use the full suite of tools in the 4e toolbox: for combat, I liberally used minions and swarms to reflect low level NPCs/creatures; in skill challenges, I established fiction and stakes that matched the tiers of play - eg no epic tier PCs haggling with tavern keepers over the price of a meal.
You can't make a FRPG simple, yet high power, and stick to D&D conventions for how actions are declared and resolved, how combat is handled, etc.
A game like Agon 2e is simple, and can be high-powered. But it completely avoids all the D&D-isms. Its play is almost nothing like a wargame.