Where you end your turn matters: Be aware of the number of connected Locations that you will have to place Minion tokens on during Step 4. Some Locations only have 3 connections and some have 7!

Don't ignore Location powers: The 5 Locations with powers can have a huge impact on the game. They can easily turn a bad turn into an amazing one. Use them often.

Have a strategy for sleeving: Leaving a card un-upgraded makes it a good choice to discard if it can trigger a powerful effect. Depending on the cards in your deck, it may make sense to sleeve multiple upgrade cards into 1 very powerful card, OR spread them out over several cards.

Knuckles is the MVP: Knuckles can go to Locations you can't reach and never takes Damage. His ability to stop Minions from entering a Location can make a huge difference if you place him wisely.

Sharing Locations is mixed: Drawing the extra card for ending your turn on the same Location with another Character is powerful, but it increases the chances that if Minions move, they will come to your Location instead of being split between multiple Locations.

Be aware of the Villain powers: Adjust your strategy to compensate for the Villain's Skull powers, especially if they have unlocked any powers.