Before everybody on these forum starts crying about SkyRe being nowhere near the best mod out there, consider that SkyRe
is currently the #1 in the most recent endorsemants list, so the title of this topic is perfectly justified.
I've been using SkyRe for about 100 ingame hours now on various different characters, although they always end up as some sort of spellblade. You haven't really stated what you want to know about the mod, so I'll just say I like it a lot, but I use nowhere near all of the modules (basically only Main, EnemyScaling, EncounterZones, and sometimes Races, and compatibilty plugins where applicable). If you have more specific questions, I might be able to go into more detail.
As for compatibility, SkyRe provides patches for most popular weapon mods, OmegaRed99's Armor mod, and Morrowloot (maybe a few more I forgot). You can detect basic incompatibilities with common sense, if a mod changes something that SkyRe affects as well, there will most likely be a conflict. Problems I have run into myself include new ingredient mods (conflict with SkyRe's alchemy system). If you have any mods that modify leveled lists, a conflict is also likely, but that can be alleviated by utilizing a Bashed Patch (http://www.gamesas.com/topic/1392055-rel-wrye-bash/). Mods that change races conflict with the Races module, vampirism mods conflict with the Vampirism module, etc.