The problem with the current Curse system is that all of the Cursers (Mountebank, Witch, Familiar) are sort of must Buys, especially in 2p.
In 2p, having 10 Curses (thus -10VP and 10 crap cards which clutter your deck) is totally unworkable and it's basically a race to the Curse cards, a race down the Curse pile and then the real game starts.
Anything that makes the current Cursers more of an option than an unescapable truth gets my vote. Sure, Ambassadors help and so do trashers, but with 2p. the Curser + Trasher still has the upper hand over the Cursee + Trasher, since the Trashers aren't always drawn with the Curses in hand.
I like the mixed Curse/Action or Curse/Treasure cards which players may choose to get instead. They may be willing to get extra -VP as long as the Curses aren't entirely useless. For this to work, I think 10 cards from the normal Curse pile (which means everything in a 2p game) have to be mixed with normal Curse cards (or just do half-and-half) to keep the normal 3-pile ending condition intact.
Otherwise, Curses may start flying and players have double the amount of Curses and there's only 1 pile left, which doesn't make for a fun family game.
Something simple like:
Tainted Water - Cost 0, Curse/Action, +1 Card, at the end of the game -3VP for every 2 Curses.
Cursed Coin - Cost 0, Curse/Treasure. $1, -1VP
I know cards like these are likely to spur some debate, but we have to look beyond what the game already offers to be able to judge a new mechanic objectively. If it were the other way around and there would be Curses like this from the start of the game, we might be saying: "Why don't we have plain Curses? We have plain Victory cards, those simple Curses would be sufficient to weigh your opponents down, now they hardly feel a sting."
Besides that, everything can be tweaked. Like with Prosperity cards (and choosing whether to include Plat/Col), you could draw a number of cards or just throw a die and only include the special Curses if you throw a 6.
I like to keep an open mind when it comes to new cards and mechanics and as long as it doesn't break the game entirely, I'm all for it.
Adding 1 other custom Card to the regular kingdom cards hardly adds even 1% to the total number of possible setups.