My short answer is: You will almost certainly regret this.
Back in the 1970s (I was in my 20s) I took a bus from Istanbul to Zagreb. I don't remember how long it took, but I think it was close to 24 hours. I also commuted by bus to college, 17 hours or more each trip. Overnight bus rides are miserable for a huge percentage of people. The odds that both you and your friend will be the lucky sort who can sleep sitting up are very low.
I regularly take long, daytime bus trips in Europe and don't really mind them; that's often the most practical way to travel between smaller cities, especially in central/eastern Europe. But overnight rides are the pits, and I now break my trips up with stops along the way when necessary to avoid a night on a bus.
As for safety, I suppose theft of you belongings would be a bit of a concern. Otherwise, my knee-jerk reaction to questions about safety in Europe is normally to say "No issue". Honesty forces me to admit, however, that my Istanbul-Zagreb bus struck and killed a pedestrian before we even got out of the city. My guess is that it was a jaywalker who materialized suddenly in front of the bus and was not avoidable, but I didn't see it happen.
Bus schedules are a bit unpredictable because of traffic. In addition, it has been my experience that bus riders do get some attention at borders in the Balkans, so there can also be delays there.
In general, the intercity buses in Europe are comfortable enough (I'm short), but a maintenance issue affecting heating or air conditioning is always possible. I took a day-long midsummer bus ride from Sicily to Puglia in a bus with broken air conditioning. A failed attempt to fix the a/c led to a departure that was several hours late.
Fly.