RPG

Rather than a specific system or style, I think the important thing is what gets you and your players excited. Pick a genre or theme that you are your players are into, then find a system that matches that. Once you get into it a bit more you can start digging into different styles of RPGs because you'll have more context for what it all means and some idea of what you all like.

I like rules light systems because they've got a shorter "time to table", but if everyone is very excited to play DnD, then DnD works because it'll keep everyone motivated and engaged.

Some ideas:

Sci fi horror game along the lines of Alien: Mothership

Hardscrabble, fools forced to delve into dangerous dungeons and weird woods to make a living: Cairn

Grannies solving murder mysteries a la Miss Marple: Brindlewood Bay

A gang of thieves in a Dishonored-esque whale oil powered city: Blades in the Dark.

A gang of thieves flying a space ship in a star wars or firefly styled galaxy: Scum and Villainy

A doomed world undergoing heavy metal apocalypses: MÖRK BORG, or CY_BORG for the cyberpunk version of that.

Buffy and friends taking down vampire threats, or Mulder trying to find the truth that's out there: Monster of the Week

Personally I've had really good luck introducing new players with Mausritter. The physical version is gives people a tactile card based inventory, the digital version is totally free. It's super easy for people to get into the head space of tiny mice! There are also tons of fantastic modules to run which makes your job as a DM a lot easier.

This comment got a bit away from me, but I've run and played a ton of different systems, so if you have some idea of what you think you and your players will be into I can maybe point you in a more specific direction.

I am either very interested in trying, or have tried and enjoyed basically all of the systems I see mentioned so far.

A personal favorite base system of mine that counts as pretty rules light that I might also suggest here, would be the Tiny D6 line of games from publisher Gallant Knight Games.

They have a simple base d6 system that is really easy to learn, and then lots of setting/genre books that take the base system and add just a bit to it to make it fit thematically. The whole line is also super modular, so you can take additions from one book and pile them onto another one to dial in closer to the theme you're aiming to hit for a campaign. All of the base books are full systems, so you can buy any one of the main books and be ready to play. The one book covers the DM/GM and however many players.

• Tiny Dungeon is the base fantasy system and covers typical high or low magic fantasy with swords and shields and the like.
• Tiny Cthulhu adds the horror element and a corruption mechanic, as well as suggestions for Pulp and Noir.
• Tiny Frontiers: Revised makes everything Sci-Fi and adds in giant vehicle (space ship) mechanics.
• Tiny Mechas and Monsters: Evolved takes the Sci-Fi and throws in giant mechs fighting giant Kaiju monsters, where the players can play as either side.
• Tiny Supers takes the base system and throws in super powers as options in building characters, and provides guidance on how many powers to grant characters to fit the "level" of the supers. Be it neighborhood, city, national, galactic, etc.
• Tiny Taverns is a big social bit, of the characters staying in one place running a tavern or other shop, and largely interacting with just one town
• Tiny Gods starts with the group (GM and players) working together to create the world and the races in it, then has suggestions for playing in that world as a demi-god, or you can jump to any of the other books to play in the new setting you've created.

Then they have many more that I haven't even broken out here: Wastelands, Gunslinger, Pirates, Zombies, and even more I can't think of off the top of my head at the moment. But you learn the main dice mechanic, and you know 80-90% of what you need to play any of them.

But it definitely sounds like you already have a good place to start selected, and lots of really great options to investigate from there! I hope you all have loads of fun, and don't feel compelled to stay tied to any one system, feel free to change it up from campaign to campaign, or to throw in one-shots as breaks in longer running campaigns. Sometimes those one shots can help keep players excited, or help provide a bit of a mental reset between story arcs!

I would opt for a homebrew setting on an earth-like world. The reason is that, having the world be earth-like means there won’t be any misunderstandings about the basic rules of the physical world. Using your own setting means that you won’t have to fight up hill against any assumptions people might have with regards to cultures in that world.

Honestly, the way I see it, it might be good to play something you are interested in keeping playing. It may be just my experience, but I see a lot of system and genre inertia, where the players aren't willing to switch systems that easily.

Familiarity with the world lore will be more important in the long run. In the short term, remember that players want to play, they want to buy into the world, or, as Matt Colville put it, they have "willing suspension of disbelief".

As a sidenote, if you want to play D&D 5e or similar tactical medieval fantasy games, i strongly suggest watching the Running the Game videos in Matt' YouTube channel (found here). Start from the beginning, he takes you step by step in designing a first dungeon to dip your toes in the DMing water.

Welcome to the hobby!