Here's a few things that increase the difficulty...
- Use MM3/DSCC design numbers and philosophy. The monsters all hit harder (even if some of them hit less often, like soldiers), are easier to hit, and have cool effects in place of resistances (like dealing damage right back when you hit them with the wrong damage type) or when bloodied (auto-activate powers as well as new powers becoming available).
- Never throw an easy encounter at them. The DMG has guidelines for what constitutes an easy/moderate/hard encounter. Stick to moderate and hard.
- Make it difficult for the players to have extended rests by limiting the number of safe places they can take an extended rest. In my latest hexcrawl, they have to get to a hex that has a safe place (friendly town, special location like an enchanted meadow, etc) before taking an extended rest.
- Use terrain against them as much as possible. Since you're setting up the battlefields they will be fighting on them, put them at a disadvantage. Use enemies that can easily move the players into hazards or difficult terrain. Include terrain features that add powers, and have the monsters use them ruthlessly against the players before even touching their own encounter/recharge powers.
- Overwhelming damage in one encounter can crush the party completely, since they are limited in the ways they can spend a healing surge during an encounter. Everyone has Second Wind, which allows a healing surge value worth of healing and a +2 to Defenses until the end of your next turn... but it means you give up an attack for a round. Healers have a twice (or thrice, later) per encounter heal that adds some bonus healing and/or an additional beneficial effect built in, and some more heals scattered around their power lists. Healing potions and such are still around, but they eat up healing surges and usually give you back less hit points than your surge value.
- Remember that healing surges are the "second layer" of hit points.
Neonchameleon's thread on hit points and healing surges is a good resource for understanding how they interact and how this can be displayed in game. Creatures that take away healing surges with successful attacks are scary. Between increased damage and surge removal, a full powered party can leave their first fight in bad shape.