If fl2000 is master of seat only llvmpipe can be used for rendering.

[Lassebq]

output of loginctl seat-status seat1

seat1
Sessions: *20 5
 Devices: n/a  
         ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7
         │ usb:1-7
         │ └─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3
         │   usb:1-7.3
         │   ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.1
         │   │ usb:1-7.3.1
         │   │ ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.1/1-7.3.1:1.0/0003:09DA:C10A.0005/hidraw/hidraw4
         │   │ │ hidraw:hidraw4
         │   │ ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.1/1-7.3.1:1.0/0003:09DA:C10A.0005/input/input28
         │   │ │ input:input28 "A4Tech USB Mouse"
         │   │ └─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.1/1-7.3.1:1.0/0003:09DA:C10A.0005/input/input29
         │   │   input:input29 "A4Tech USB Mouse"
         │   └─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3
         │     usb:1-7.3.3
         │     ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.0/0003:1A2C:6004.0006/hidraw/hidraw5
         │     │ hidraw:hidraw5
         │     ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.0/0003:1A2C:6004.0006/input/input30
         │     │ input:input30 "SEMICO USB Keyboard"
         │     │ ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.0/0003:1A2C:6004.0006/input/input30/input30::capslock
         │     │ │ leds:input30::capslock
         │     │ ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.0/0003:1A2C:6004.0006/input/input30/input30::numlock
         │     │ │ leds:input30::numlock
         │     │ └─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.0/0003:1A2C:6004.0006/input/input30/input30::scrolllock
         │     │   leds:input30::scrolllock
         │     ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.1/0003:1A2C:6004.0007/hidraw/hidraw6
         │     │ hidraw:hidraw6
         │     ├─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.1/0003:1A2C:6004.0007/input/input31
         │     │ input:input31 "SEMICO USB Keyboard Consumer Control"
         │     └─/sys/devices/pci0000:00/0000:00:02.1/0000:02:00.0/usb1/1-7/1-7.3/1-7.3.3/1-7.3.3:1.1/0003:1A2C:6004.0007/input/input32
         │       input:input32 "SEMICO USB Keyboard System Control"
         └─/sys/devices/pci0000:00/0000:00:08.1/0000:06:00.3/usb4/4-2/drm/card2
           [MASTER] drm:card2
           └─/sys/devices/pci0000:00/0000:00:08.1/0000:06:00.3/usb4/4-2/drm/card2/card2-VGA-1
             [MASTER] drm:card2-VGA-1

As you can see drm:card2, which is fl2000 dongle, is the only "GPU" which drives this seat. My system has a render-capable GPU on seat0, which is AMD Radeon RX 580 and the second one is AMD Radeon Graphics (renoir) from CPU (Ryzen 5 4600G).

In a configuration where Renoir is on seat1 and RX 580 is on seat0 then I'm able to render applications using RX 580 by setting DRI_PRIME environment variable. Same configuration but with Renoir replaced by fl2000, it uses software rendering for compositor (which is fine and probably expected) and applications seemingly ignore DRI_PRIME and instead fallback to llvmpipe. I could get some info from vkcube running on xcb backend which said: No DRI3 support detected - required for presentation
In an attempt to run anything on vulkan using wayland backend the whole compositor crashes.
In case of OpenGL applications (GLX and EGL) neither of them provided any useful information regarding GPU selection. It forces llvmpipe for rendering

To clarify, I'm using fl2000 as a cheap alternative to Multi-GPU multiseat - https://wiki.debian.org/Multi_Seat_Debian_HOWTO

[Lassebq]

I know this is a pretty complex problem so it probably needs addressing from other big projects like Mesa and/or GNOME mutter team

[Lassebq]

I managed to stitch a fix for Mesa. PRIME rendering works, it's just the logic which didn't account for primary GPU having no render node.