I hesitated over the reroll feature for the first few games, until I realized I wasn't getting past level 3 anyway so there was no need to preserve resources--at which point I learned that it's three rerolls per upgrade, not per game. Once I knew that, I started using them more, and it did help somewhat. Of course, once of the things about the synergies is that swapping cards not only means "pick up a vampire and hope you start getting more", but "give up a ghoul/tenement to get it", which was a small blow to the existing synergies in the deck....
Knowing the vampires/#blood thing definitely makes a difference! By the time I encountered the vampires, I'd internalized the rule about rivers being "if they're connected to the original blood source" and hadn't thought at all about their literal text.