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For general installation instructions, follow this guide.
While trying to get Titan Quest: Immortal Throne running on my son's computer, I ran into a number of debug problems. To fix the first, related to libudev.so.0 (install libgudev1 if it's not already installed):
$ sudo ln -s /usr/lib/libgudev-1.0.so.0 /usr/lib/libudev.so.0
If your application is 64-bit, then run the following:
$ sudo ln -s /usr/lib64/libgudev-1.0.so.0 /usr/lib64/libudev.so.0
The other errors were as follows. Most, if not all of them, relate to sound.
err:module:load_builtin_dll failed to load .so lib for builtin L"winepulse.drv": libpulse.so.0: cannot open shared object file: No such file or directory
err:module:load_builtin_dll failed to load .so lib for builtin L"winealsa.drv": libasound.so.2: cannot open shared object file: No such file or directory
err:mmdevapi:DllGetClassObject Driver initialization failed
err:ole:apartment_getclassobject DllGetClassObject returned error 0x80004005
err:ole:CoGetClassObject no class object {bcde0395-e52f-467c-8e3d-c4579291692e} could be created for context 0x1
err:dsound:get_mmdevenum CoCreateInstance failed: 80004005
The problem is that Titan Quest is a 32-bit application, whereas the WINE-PulseAudio system is 64-bit. That's why sound doesn't work. To fix it, install the required 32-bit libraries:
$ sudo yum install pulseaudio-libs.i686
Colors and Textures
If you experience screwed up colors and textures, check the PlayOnLinux debug log for the following error:
err:winediag:wined3d_texture_init The application tried to create a DXTn texture, but the driver does not support them
To fix it, try installing the following 32-bit package:
$ sudo yum install libtxc_dxtn.i686
See this AskUbuntu page for more information.
Firewall
I also found that firewalld was blocking multiplayer connections. To allow for LAN games, open firewalld (search for firewall in GNOME), switch to the Protocols tab, and add udp as a protocol. To make this change permanent, go to the Options menu and select Runtime to Permanent.