I was hoping to hold off on this until I'd had a chance to test it out, but most of my gaming with actual cards has been 3 or 4 player over the past month or so.
It was an idea I'd first come up with for a 2-player Ticket to Ride variant, and I thought it would carry across well to Dominion.
The idea is to play with two decks/hands/discards/everything, as if you were playing a 4 player game. Your score at the end is determined by your highest point value minus your opponent's lowest point value (so you can't just elect to tank with one of your decks, they have to both do reasonably well).
What does everyone else think?