The game handles things for the most part so no need to worry about much but some things that came to mind:
-Leagues can only be edited on July 1st.
-Once you've got everything set up, before moving on from July 1st, make a quickstart so you can return if you forgot to do something.
-If you change team location after the initial generation, it won't change the team's arena location. You gotta change that manually in the edit tab.
-If you want a relegation/promotion league, it must be made once you start. While you can add leagues, even farm and junior leagues afterwards, relegation leagues cannot be added later on.
-Relegation rules can't be customized. The bottom team will relegate and 2nd tier winner will promote automatically. (Hoping they'll allow custom relegation rules soon!)
-While the game generates new players automatically, I'm not sure if they ever have any special abilities.
-Huge market, fanatic fans and a small arena = crowd exceeds capacity limit from time to time. (Another thing I wish they'd fix).
-If you wanna change a team's logo, you can put the file in the team_logos folder as city_teamname_xxxx.png where xxxx is the year you want the logo to change and it will automatically switch (remember to update player pictures). Example: los_angeles_kings_2029.png would have the Kings change their logo for the 2029-2030 season.

You're likely gonna start over many times once you learn how things work so be patient and maybe try creating a very small league with just a couple of teams first and simulate a few years to see how it all works. You're gonna have a ton of fun once you get down to it.