Unless you want to design a universal game like GURPS (Generic Universal RolePlaying System), one of the first decisions you have to make before you even begin to design, is settling on a genre or theme. A system usually reflects the genre of its game: for instance, Tephra is a steampunk TTRPG that is based around the d12 (12-sided die), because the number 12 and clockwork kind of go together.
A whacky space opera will require completely different mechanics than, say, a crime noir set in a 50s inspired world, and both will in turn be different from heroic high fantasy. A mechanic for space flight and FTL shouldn’t go amiss in space themed systems, but would be wildly out of place anywhere else. Likewise, a system centered around criminals and heists might have a heat mechanic.
The genre of your game might also help formulate what kind of abilities player characters can have. Medieval fantasy might have little use for a high tech engineer, but could have magic users aplenty.
Another important question is this: do I want this system to work in one setting, and one setting only? Or am I designing for a whole genre? The latter will have to take many different eventualities and sub genres into account while the first will potentially lack the adaptability for homebrew or third party settings.
But all this is not written in stone: of course you can have space druids and fantasy engineers, if you build the mechanics for it. Deciding on a genre doesn’t mean you have to limit yourself; it just means you have something to work off of.