You don't reveal what your experience level is. Are you a new rider? Have you had many bikes?
My advice is to buy what your going to find more fun.
I've owned lots of bikes. I've only been riding over 15 years. I have both these Honda engines in cb***f models.
I bought the 300 Rebel and added it to my collection because it is more fun. The 300 can do everything the 500 can, granted maybe not as quickly. I would counter the "saftey" argument for the 500 with... "THINK!"
You don't have to put yourself in stupid situations. You could just be a careful and smart rider. People will always make an argument that you need a bigger engine to be safe. That's Bullocks. There will always be bigger engines and bigger heavier bikes than whatever you own.
Look at the 300,000 happy Grom owners. Just try to find a single review of that tiny bike that doesn't have the word fun in it. Those guys are on to it. They get it. Granted they aren't running down the highways but the truth is, the 300 Rebel will do ya just fine on the highway and carry you on your trips. That is, as long as you don't have to ride 90 mph into a head wind down a featureless interstate trying to make time.
That's not a trip. Correction, that's not a fun trip. And that's my point. Buy what is fun for you. If one doesn't have much experience or confidence the 500 probably would make a better choice for some.
But if you're like some and you know what you're doing I'd go with the smaller lighter 300. When people argue a heavier bike is better for high speed interstates it always makes me grin. I enjoy being pushed over by the wind when a huge truck roars by. Who really doesn't? It's not like you can't compensate for a brief moment and go with the flow to let it widen your grin.
Anyway, these are just my opinions on the 300 vs 500 issue. Go test ride both bikes if you can. Then you'll know. You'll know which one makes your heart race. That's the one you want.
I am not trying to be mean here, but your post has so much wrong with it.
1. The 300 is more fun? The bike is barely lighter, and has quite a bit less power. How on earth is it more fun?
2. "Don't put yourself in stupid situations" Believe it or not no matter how careful of a rider you are, it doesn't stop other terrible drivers from doing things that put you in danger. A bigger engine being safer isn't bullocks, it is a fact if you are a decent rider.
3. "People argue a heavier bike is better for high speed interstates." You know who doesn't like having wind knock your bike all over the road? Basically everyone on earth. Heavier bikes are better on highways and interstate, and that is another FACT. But the Rebel 500 will not really have an advantage as far as not being blown around compared to the 300.
4. "The 300 can do everything the 500 can but not as quickly" The speed and power difference is literally everything, so saying that makes no sense. And beyond that the 500 will do everything the 300 can smoother.
Neither bike has ungodly power and speed, they would both be fine for a beginner. But the fact is the 500 can do everything the 300 can.... but better.