I wouldn't mind the "Dominion has an end" thing so much if there weren't so many unexplored opportunities. Everyone I play with loves duration cards; why were they only produced in one set? Alchemy got worse reviews than the other expansions because it introduced potions without a lot of cards that used them; why not make more cards that benefit from them?
Adding to that, it seems many sets have some sort of "gimmick" that isn't a part of the core game. Seaside and Prosperity both had game tiles and tokens, and Cornucopia had Tournament prizes and Young Witch's Bane pile. Alchemy, as mentioned above, introduced potions. If you're going to add new game mechanics with each set anyway, why not continue to make new sets with new mechanics?
The core mechanics may be simple (and that's admittedly the primary draw of the game), but there's still a lot of opportunity for expansion. You play around with unorthodox concepts like controlling other players' turns (Possesion), taking additional turns (Tactician and Outpost), stealing cards (Masquerade and Thief), using additional Supply piles (Black Market, Young Witch, Tournament), free but limited action use (Throne Room, King's Court, Golem), etc., but you never really explore them as much as you could. At the same time, there are too many "one-offs" like the cases mentioned about to give the "we've run out of ways to modify the game" argument any validity.
People make and play fan expansions, so clearly there are ways to add to the game that you haven't considered yet. Why not continue developing and let the game evolve?