The Binding of Isaac

Edmund McMillen and Florian Himsl's The Binding of Isaac builds its entire roguelike loop around item synergies, individual pickups are often unremarkable alone, but combined with the right other items they can completely transform how Isaac's tears, movement, and abilities behave.

Because a run's items are randomized and permanent for that run, taking an item you don't fully understand yet is usually worth the risk, since even a seemingly bad pickup can become powerful once paired with something found later. Clearing a room fully before moving on tends to matter more than rushing toward the next item, since incomplete rooms often hide the resources a harder floor further down will demand. Die in the Dungeon covers similar dungeon-roguelike ground with dice-based combat replacing item synergies.