It’s really not that complicated. The only other direction to go on I-65 is north.

Interstates with odd numbers run north and south. Even numbers run east and west.

I think it is usually multiples of 10 as well so for example I-5 runs from the border in San Diego (or close enough) to the border with Canada. I-10 runs from LA in California to Jacksonville Florida, smaller routs ending in 2, 4, 6, or 8 are small sections that terminate a few towns over usually or connectthe bigger highways to eachother.
Ah, interesting. The number of digits means something too. 3-digit numbers are… Some other kind of routes. I’m too tired to remember exactly 🤦🏻‍♂️
Basically, routes meant to serve a metro area/region instead of being actually cross-country. Think ring roads around cities and whatnot.

Nah.

Around here I-76, I-78, I-80, I-84 (what happened to 82? I don’t know); are all major roads that go through multiple states

Going the other way 81, 87, 95 are all significant

They could be major in your local area and go through multiple states but the big ones ending in 0 or 5 tend to go across the country. And I-80 and i-95 would fall into that category, if those roads stay in a lower tier or get expanded later is another story.
The way I always remember is both North and South have an odd amount of letters (5), and East/West have an even amount of letters (4).
Sure, but use Google maps and have a look at “i-435”
And I thought I-45 being an “interstate” that only exists in Texas was bad!
There are interstates in Oahu if that helps, ha ha
Also Alaska and Puerto Rico! The interstate signage is more about the funding source than where the highway actually goes.
Three digits starting with even are loops, starting with odd are spurs. Thats why I-495 can be both the capital beltway and loop around boston
Three digits are auxiliary routes. Some are loops, some are spurs, some are… Something else. I don’t remember the specifics, but there are more details to the auxiliary routes.

Similar overlaps over in NY with 87/287, and 95 does something shifty near there also.

BTW there are multiple I-495s and 2/5 are Spurs

Oh yeah, I always hated that. I used to visit my ex’s parents down in that direction and I knew the way from having driven it every year but if I tried to give directions I never could remember which is 287 and which is 278
In what world is that not complicated
How could it be less complicated?
I’m a flight instructor, have been for over a decade. Ask me how VORs work. In my world, highway numbering is not complicated.