Synergies Mod is an example of a mod with great ideas, but packaged with too many changes. The net result is that you might want some of it, but not all. In a way, you're back to vanilla Torchlight 2 -- A sort of all-or-nothing situation. Very large mods do tend to be released in a sort of convenient single package, but this really defeats the purpose of the modularity of mods. (Torchlight 2 does have a 10-mod limit, so this does tend to encourage compilations, however).
One of the interesting ideas here is "elite" and "hero" non-champion enemies. You could randomly encounter them, and they don't have special abilities like Champions, but are tougher. Some are tediously big and tough, however, like Hero Warmakers with a huge amount of health and an irritatingly high block rate. They are big and neat to see the first couple of times, but after that they are just boring and tedious to grind through. It slows the pace of the game down, and wastes your time handling one tedious and unimportant enemy.
Another interesting idea is "world bosses" -- super-tough boss enemies. Again, an interesting idea, but they could block your way in game story progress and then you have to wait for the world to respawn (you can force a reroll of the game world in single player by starting a LAN game and checking the Reroll box). It's not for everyone and could be a gamestopper. It's packaged with Synergies, so it's likely a lot of work to take it out if you even want to fool around with the mod editor.
Yet another idea is increasing the number of enemies that spawn, increasing their health a lot, and simultaneously reducing the level requirements for skills. This accelerates your game slightly in terms of level advancement and seeing skills, but I feel the cost is too much -- too much grind just killing the enemy hordes. Also, the amount of health combined with the increased amount of enemies means area effects and crowd control are suddenly much more important.
The amount of items that drop simply because there are more enemies increases, but it's generally just more junk because the rate of good loot dropping hasn't been increased. If you do play Synergies, you might want to get something like a Bag Mod to reduce the amount of time you send your pet to town.
Despite the increased enemies, you may find the game not appreciably harder than regular Elite mode, and possibly easier (e.g., my Engineer playing Synergies on Elite difficulty finished Mordrox of the Bring Out Your Dead quest using no potions, but in vanilla Elite mode had to use a few healing potions). But the pacing is definitely slower.
New classes such as the Necromancer, and lots of pets, are added in Synergies and more work is being done on them, so if those are of interest to you it's worth watching to see how things develop.
Some mods that modify Synergies include a loot drop rate mod (which doesn't seem to do that much) and a population control mod (which seems to also disable the skill unlock level changes -- but you can get that back with this mod).
You can also ease the getting-to-the-Enclave start of the game by using a Heal Self I or Heal All I spell. To spawn it (since you can only get spells from loot until Act II), use the single player console and the allitems spell command. This creates all spell scrolls at your character's location. Take the one you want and reset the game world, or put it in your shared stash (which you can access anytime if you have the BagMod) for another character to pick up.
Overall I decided not to use Synergies, and instead went back to choosing more modular mods and in that way have greater control over tweaking my game.