without the long story about the 5 hours wasted on checking and rechecking the configuration to find later that all the new settings or modifications had no problem and all that was required was a reboot!!!

I found several posts by others stating the same situation. The router should at least indicate that a reboot might be required for some changes to take effect. I'm posting this question for my sake and the sake of all the other users:

After which modifications is it required to reboot a Mikrotik router for changes to take effect?

I have two RB450G's in service running ROS 6.18. I also have RB750GL test unit running ROS 6.24. I think I started at ROS 6.4 or 6.5. It has not been my experience that they required a reboot for changes to take affect. I have found if you delete something (not using safe mode) by mistake, you better have a backup or know what you just deleted.
After I reboot them for an upgrade, I always reboot them again.

The short answer would be "never", all changes are applied inmediately.

But for example, if you were dealing with NAT rules, those rules are only checked on the first packet: if a connection is already stablished those rules won't be checked until the connection times up (/ip firewall connections). I have seen something similar with IPsec, having to disable/enable the related configuration items to force the router to flush settings.

There is no need for a reboot of the router to save the settings and changes that you made. They are saved on the fly as you made them.

Unused marks will not disappear until reboot. For example.

Unused marks will not disappear until reboot. For example.

Of course, but that doesn't affect the configuration in any way, they are just unused. The point being, you do not need to reboot the router when you do some changes.