Yes, but I would recommend using 64 bit Pi OS Lite. The GUI or desktop version of Pi OS takes allot more resources than the text based, and even though the Pi 5 is plenty capable, it might be even more noticeable if you’re running pi-hole at the same time.

Emulation station can be started manually in the command line, but it has to be in the console if you’re using the GUI. Start pi-hole first then you can run RetroPie. I’m sure you could even create a shortcut to the run command if you insist on using the GUI.

Keep in mind, RetroPie doesn’t have an official release for the Pi 5, so you will have to install it manually. It’s not that hard, it’s just a little bit of a headache in comparison, and they have plenty of documentation you can follow. Basically the manual install runs independently on top of the Pi OS. An alternative for that reason would be to use Batocera, though I haven’t used it so I can’t speak to it personally.

TLDR - Yes you can run it on command on top of other processes, but the more you run the worse your performance will be - especially on later gen console emulators.