I've seen guys make:
-Incredibly detailed pantheons of gods with unique spells, dress, rituals, etc. for each one
-Unearthly worlds like one where it was set on hundreds of tiny moons in a vast cloud of air and people used flying boats to travel
-Unique systems of magic that required effort and roleplaying to work
Great stuff! Very creative, very memorable. I have a lot of things like unique days for the names of the week that are still recognizable [Sunday, Moonday, Twoday, Threeday, Fourday, Fiveday, Starday], unique constellations, etc. And the players do like them, especially when they are dropped into play aids
"This journal entry is from the 2nd Starday in Midsummer of last year"and such.
But I do find that, to my chagrin, even the effort behind my unique systems of weights and measures, the unique languages, the detailed calendars, the festivals, the monsters, the NPCs the most return for the least effort appears to be - mundane plants and animals.
Here's an example from my Seaward (AD&D 1e) campaign.
Along the southwest border of the Kingdom of Seaward lies an area called the Briars. The Briars cover the foothills of the southern mountains in addition the the very rough, rocky terrain large areas are choked with briars and brambles. The region is home to some plant and animal life either rare or absent anywhere else including the briar wolf, the briar deer, the brush cat, the hill tortoise, and the hyrax (or the 1/2 normal hit dice deer, the jackal, the lynx, the tortoise, and the groundhog). Plants include scrub pine, juniper, the evergreen oak, the lemonade bush, and the strawberry tree.
Now, when I wrote up the area and its encounter charts I thought the weasels, giant rats, mountain lions, and kobolds would be the memorable parts.
The players all remember (and talk about) the lemonade bushes, the strawberry trees, the brush cats, and the evergreen oaks.
I chalk it up to the effect Heinlein so famously described many years ago about how little things set tone. You can describe mile-long starships all you want but 'the door irised open' really drives home how different things really are..
So - work on the little things, the odd little bits like green house cats and such. It seems to be memorable.