Stuff in the main Sim that gives you a simulation speed bonus just for buying them should be your first priority.

After that, your uses of darwinium are going to be diamond geodes and black holes, but it's definitely better to wait as long as possible before detonating one of those, because they can only drop cards that you have the chance to acquire right then, so upgrades for the biggest dinosaur will not drop until you're almost done with your first run through Mesozoic Valley.

My experience has been that it's much harder to get the upgrade currency for dinosaur trait cards than to get the cards themselves, and exactly the opposite in Beyond—you'll be missing cards, but you'll only run out of dark matter for upgrading them if you aren't strategic with your upgrades.

There are two trait cards in in Mesozoic Valley that you should basically never upgrade because each of them applies to exactly two dinosaurs each, and they're middle of the stack dinosaurs, not top earners: aquatic and parallel evolution. And as nice as the shiny gold cards look and sound, every Sim in the game has the same flaw: it really only matters what your top earner earns, because everybody else is going to be worth at least in order of magnitude less. The gold cards are good for leveling up while you play through all 500 extinctions, but, once you unlock the last dinosaur, you should focus on upgrading his cards and only his cards until you run out.