I have a Warden in the game I am running and he is nasty. It is not his mark that does the most damage, but it's the Warden Forms that do it. When he creates difficult terrain around him, enemies have a hard time getting away without being whacked. The Warden also is very durable, so even focusing fire on him doesn't help you much. Your best guess is to attack his weaker defenses and daze or stun him. That requires monsters that can actually do that, of course.
Aside from this, not all Defenders play the same.
The Fighter and the Warden are typically the type of defender that move to their foes and then keep them there, be it with their mark abilities or with their powers.
But beware: If the enemies somehow gets away, don't stand around complaining, follow them and keep them busy. It doesn't hurt to stay close to your weaker allies, if there are no obvious bottlenecks that you can defend.
The Swordmage is typically a lot more mobile. His mark usually works best if he engages one foe and marks another. Basically the enemy has to follow the Swordmage or suffer the consequences of the mar.
The Paladin basic mark has the big advantage that it is automatic damage - no actions, no attack rolls, it just hurts the foe. A fighter still has to hit and needs immediate actions or opportunity action to work his shtick. Sometimes that's easy, sometimes it is not. It doesn't hurt to boost the damage of your Divine Challenge, obviously, especially for Strength-focusing Paladins. But a lot of other defender abilities for the Paladin come from his powers, and there the devil is in the detail. (More so than for the Warden, by the way. The Forms are pretty much like the Barbarian Rages, a lot more straightforward).
Lay on Hands is a defender feature for the mark in two ways - for one, he can compensate other allies getting hit when he "fails" (or the enemy choses to ignore him). If the enemy focuses on him, he can help himself.
An important part for a Defender is to identify the threats that hurt the party most. That is often a Brute, but sometimes keeping a Soldier busy is really useful to the rest of the party, too - because then they are free to attack the targets that really inflict the damage. Skirmishers and Artillery monsters are probably hampered the most by a defender, but Artillery is often hard to catch when the enemy can establish a front line of melee focused creatures. Lurkers typically have too many "get-out-of-jail" cards, but they can be the right target for a Swordmage or Paladin, who can work their mark at range.
Most defenders need to team up with party members that are also good in melee and stay close. It doesn't matter if the enemy can walk around the fighter if he still has to stay within 2 squares of him to strike one of his allies. The Fighter (or Paladin, or Warden) can shift to him, mark him, and now the enemy is locked down. (The Swordmage doesn't need or want to shift, probably.)