Do you get change from cards in Ascension?
You can buy 2 cards costing three runes each, but not because you get "change".

When you play a card worth 2 runes, what that does is adds 2 runes to the pool of runes you have available to spend. So when you play 3 cards like that, you now have 6 runes in the pool of runes to spend. It no longer matters at all how the runes got there. You have 6 runes to spend, and you can spend them however you like.