I'd recommend posting in the heavy duty section also. I have a 2014 2500 with the 6.4 and have had no issues with the engine. I had shift solenoids go out around 2500 miles for the transmission that put the truck into limp mode. It was fixed under warranty with no mechanical or electrical issues since. I now have 30,000 miles on the truck. The only continuing problem I have is with the navigation system GPS not working correctly. Just annoying that I have to use my phone for GPS.
My truck does make a ticking/knocking sound when its cold out (below freezing) on the first start. It lasts about 3-4 seconds. I had a little bit of lifter noise until I ran two gas tanks of Redline SI-1 through. I did that about 15,000 miles ago, and the engine is super quiet now. I'm not sure if it was the Redline or just putting more miles on the truck, but it's quite now. The Ram is a lot quieter than my previous 2013 3.6L jeep. That thing sounded like a sewing machine.
In my opinion, if I was to go shopping tomorrow for a 6.4 Hemi and it ticked or knocked for more then 30 seconds I'd keep looking. One thing to realize is you can also hear the injectors. I'd recommend going and listening to several new and used 6.4s if you can. As for the transmission, mine works fine. The shift point from first to second is known to be a little big, but I've not had issues with it even while towing. If I accelerate hard and then hit the brakes sometimes, I get a clunk as the truck tries to figure out what I just did to it.
Drive a few, see what you think. I personally believe the reliability is there and that is why I purchased mine. I plan to have this truck for at least 10-15 years and then hand it down to my son. In the heavy-duty section, there is a "how many miles" thread.
https://www.ramforum.com/threads/how-many-miles-on-you-6-4-hemi.100126/ . Best of luck.