Ubuntu 20.04 with official Zabbix Apt Repo

Obviously I can comment out ControlSocket= in zabbix_agent2.conf and everything will become OK but this file is a part of package and shouldn't be altered by user without a good reason.

Thank you for reporting the issue!  Handled over developers for fixing.

General Zabbix parameters like ListenPort, ControlSocket,ListenIP - if they should be re-defined in the included file - should be commented into the general configuration file - there is no bug
Zabbix reads the configuration file and included files and defines parameters once only, so similar parameters with the other values defined will be ignored

OK, lets experiment.
Content of /run/za2/zabbix_agent2.conf:
    PidFile=/var/run/zabbix/zabbix_agent2.pid
    LogFile=/var/log/zabbix/zabbix_agent2.log
    LogFileSize=0
    Server=127.0.0.1
    ServerActive=127.0.0.1
    Hostname=Zabbix server
    Include=./zabbix_agent2.d/*.conf
    ControlSocket=/tmp/agent.sock
    Include=./zabbix_agent2.d/plugins.d/*.conf
It is a copy of original zabbix_agent2.conf without comments and empty lines and with "Include=./zabbix_agent2.d/*.conf" instead of "Include=/etc/zabbix/zabbix_agent2.d/*.conf".

Content of /run/za2/zabbix_agent2.d/agent.conf:
    ControlSocket=/run/za2/agent2.sock
    DebugLevel=4
    Hostname=
    ListenPort=20052
    LogFile=/dev/stdout
    PidFile=/run/za2/agent2.pid

Run agent2 from command line:
    zabbix_agent2 -foreground -config /run/za2/zabbix_agent2.conf | grep -P 'listen|control'
Output of command above:
    2022/06/26 09:47:45.002711 [0] starting listener for '0.0.0.0:20052'
    2022/06/26 09:47:45.003360 cannot start agent: An agent is already using control socket /tmp/agent.sock
    2022/06/26 09:47:45.003510 listener has been stopped

As we see agent2 cannot start because distributive zabbix-agent2.service is running and listening on /tmp/agent.sock.
BTW, note that ListenPort=, LogFile= were overridden.

Now put ControlSocket= before Include= in /run/za2/zabbix_agent2.conf:
    PidFile=/var/run/zabbix/zabbix_agent2.pid
    LogFile=/var/log/zabbix/zabbix_agent2.log
    LogFileSize=0
    Server=127.0.0.1
    ServerActive=127.0.0.1
    Hostname=Zabbix server
    ControlSocket=/tmp/agent.sock
    Include=./zabbix_agent2.d/*.conf
    Include=./zabbix_agent2.d/plugins.d/*.conf

Run agent2 from command line:
    zabbix_agent2 -foreground -config /run/za2/zabbix_agent2.conf | grep -P 'listen|control'
Output of command above:
    2022/06/26 09:51:39.001175 [0] starting listener for '0.0.0.0:20052'
    2022/06/26 09:51:39.001285 listening for control connections on /run/za2/agent2.sock

Voila, ControlSocket successfully overridden and we don't need to comment out ControlSocket= in base configuration.

I remember that when I tried to do so with Zabbix Agent 4.0, it didn't allow such overriding. And I was happy endlessly when noted that Zabbix Agent2 5.0+ did. Now from your words "Zabbix ... defines parameters once only" I can conclude - it is a bug rather than longly awaited feature, isn't it.

As an (ugly) work-around, you can put your config under /etc/zabbix/zabbix_agent2.d/plugins.d/ instead of /etc/zabbix/zabbix_agent2.d/ ... Or put a symlink to your config under plugins.d/ (which will cause your config to be loaded twice, although that should be harmless).

Ticket marked as fixed/closed, unsupported version.
If the issue still persists, please create new request.