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.