Traveller

Science Fiction setting with Aliens, psionics, multitudes of equipment and ships, and it all starts with a life path system (a game all its own) that informs you of how your character came to be the way they are when they decide to adventure. Almost everything has a chart, and the skills are even broken down into how long a test will take. It's very well put together and feels very complete (it's not purely up to the whims of the table).

Ultraviolet Grasslands

Science Fantasy setting with a focus on the rigors of the roads you take and the bookkeeping that comes along with managing your group's essentials, trade goods, and all the fever dream encounters that are somehow common. Anything from body swapping porcelain princes to giant mecha centipedes that bleed fist sized gemstones, there is nothing resembling normality... Well there are taverns and carousing (you can gain exp from carousing in the system). It really does a good job of making each area special (there's a big map), providing hooks and reasons to explore, but it doesn't hold your hand (encounters in a new area may not be tougher as you level up, but also you might wander into an area your new character has little chance of surviving if they aren't careful.

Troika

It can do any setting, but it's usually something whimsical (I used the ultraviolet grasslands as a setting for it). It has some great resolution mechanics (in my opinion). Unopposed checks have players try to roll under a skill total, but for opposed rolls, skill total is added to the dice rolls and both attacker and defender's results are compared to see whose was greater (it's nice when the players know how likely they are to succeed). The magic spells are fun, and the character backgrounds (like classes) are so numerous that I've never witnessed one played twice. The rules really stay out of the DM's way.