Survivability continues to give health much longer than the other two stats. It will of course also increase your damage with survivability-scaling weapons, but those are generally hard to find and hard to use well. Usually when I go survivability I end up relying on at least a couple of golden (colorless) items
Unlocking also allows them to show up at other points during runs. From treasure chests, random drops, item shops, etc.
There are a number of things you can work toward
- Getting all the runes that open up secrets and new paths. Each rune you get (starting with the vines) opens up a path that leads to the next rune. Some of them are also useful for general maneuverability and combat, so it's good to get them all.
- Permanent upgrades at the collector. Health flask to 2 charges should be one of the first things you go for. 3 charges is also nice to get pretty soon. 4 is necessary for when you move up in difficulty level, but is expensive. The random starting equipment upgrades give you more variety at the start of the game, plus the random equipment will almost always be better than the basic starter items. Shop upgrades are very nice later on, but not too important right away.
- The blacksmith. He's the big guy that shows up after each of the first two bosses, and allows you to upgrade your chance of finding higher quality items. So instead of needing to pay money to upgrade an item to "+" quality, you can find it that way and then have the option to upgrade it to ++. It costs 50 cells for each 5% chance, and a total of 1000 cells to get a 100% chance of + quality. It's good to spend some portion of your cells here as soon as you can.
- Unlocking items. Gives you more variety and more options to work with. In particular, some of the Mutations like Sadism and Support are really nice to have. For equipment, definitely unlock the Ice Bow if you find that blueprint. Fire Grenade and Double Crossb-o-matic are two other good ones that you'll probably find early since they come from common enemies.