I have been using PlayOnLinux to manage wineprefixes on my Devuan system and decided to branch out and try using Lutris today. I have been having trouble with it since I installed CUDA (plus the accompanying nvidia drivers) from deb files instead of just using the run file. Long story short, I went back to using the run file version
PlayOnLinux is a much simpler program, and it doesn't display very well on my system recently to boot (the colors are off.) Both will download games from some common services for you, but Lutris also manages to display your game libraries. Overall POL is still useful, but it requires you to know what you're doing much more than Lutris. It is basically now on life support and not receiving changes, because it is in the process of being replaced by its Java-based successor Phoenicis. Thankfully, some people are still working to update scripts as they break, mostly due to Microsoft removing downloads they've quietly hosted for years. This can also affect winetricks, so if you're wise you'll back up your download caches if you expect these installs to keep working in the future. Both POL and Lutris offer ways to easily back up and restore these game installations, which already have their requirements installed in them; saving those backups is a good way to make sure you can play the games again someday. Disappointingly, Lutris does not save cached installation files when you cancel an installation completely, so make sure to move those to another directory temporarily if you plan to stop a large download and start it again later.
Long story short, if you are running CUDA on a Debian derivative, installing from the runfile is a convenient way to solve conflicts between CUDA's requirements and your system's packaging system. You simply dodge it.
Here's another tip that you might find handy; I have my homedir on the same SSD as my root and then I have more storage on HDD. You can symlink various directories and these programs will work correctly, which is often not a given. For instance you can create a new wineprefix in PlayOnLinux and then move the directory from .PlayOnLinux/wineprefixes to some other location and link it back to there, and it will work fine in the new location. Similarly, if you want to change the Lutris install cache location, move the directory .cache/lutris/installer to another location and then link it back, and that works too. You can even tell Lutris to cancel the download after the first file is downloaded, move the directory, and then tell it to resume downloading. It does discard any progress on the file being downloaded at the time, however. Lutris is currently downloading Shadow of War for me and the install files alone are reportedly 112.1 GB. I just don't have room for all this free on my SSD. I do see that the prices have come down considerably, however...