What I like about TL2 is that you can have multiple mods installed at once (like Skyrim, almost). So yeah, Synergies is kind of a "must-have", but beyond that you can mix and match.
There are also a LOT of "mod merge" packs out there, due to the 10-mod limit you're allowed to run at a single time. Most of these contain a ton of popular mods such as Affix Expansion, UI Overhauls, Enhanced Pets, LAO, et cetera. I personally like the "Mamba's Mod Merge" packs as they work very well with synergies, but you can pretty much pick whatever you want because almost every author makes their mod Synergies compatible.