In relation to configuration, it's alterable in all networking programs and needs to be so as networking needs change with the addition and deletion of hardware, and changes in software. Actions such as adding an ethernet device, or a wifi dongle, usually require changes to configuration files.
In addition, software that changes, makes demands on the user to learn new commands, or deal with new GUI options. Think of the differences between the older ifconfig and newer ip commands.
Then there are configuration changes that the developers make in existing programs which the user's must adapt to. Change is very common.
In relation to temporary and persistent configuration, it depends partially on the use of the computer. NetworkManager, for example, may freely alter the /etc/resolv.conf. This quote notes this feature in its help texts:
By default, NetworkManager on Red Hat Enterprise Linux (RHEL) 8 dynamically updates the /etc/resolv.conf file with the DNS settings from active NetworkManager connection profiles.
The reason it does that is because users with laptops and other mobile computers interact with many different networks. As they change location, changing DNS servers in the /etc/resolv.conf file to optimally connect to the new networks, is a functionally superior way of making the network connection for the user.
On the other hand, a desktop computer that is largely stationary at home or in an office, and connects by wifi or ethernet to a router, usually never needs to change the /etc/resolv.conf file. Rather, the contents of the file usually include the IP address of the router which doesn't change. The router does the DNS work for it, so the configuration is persistent.
The changes in configuration files don't depend so much on the tool that is used, but on how the machine is used and what its needs are. The various tools that are used to configure the network perform the same end result. Basically, it's a text editor to alter file content, or a GUI that that makes the same alterations to those files through an extra layer of software for the user's convenience.
People who I interact with on these matters note the difference between using the GUI of NetworkManager and the more command line and text editing of systemd's networking files and those of ifupdown. They go either way on the matter. Although NetworkManager does have a command line editing facility as well as the GUI, they tend towards the GUI. I guess the "major" difference is a matter of opinion.
The example above of how the /etc/resolv.conf can be treated by NetworkManager is expanded upon here:
Chapter 21. Manually configuring the /etc/resolv.conf file | Red Hat Documentation
access.redhat.com
To get a feel for the differences in configuration styles of NetworkManager, systemd and ifupdown, (and some other programs as well) in the case of configuring a wifi device, this page may help:
wiki.debian.org