Immoblize or slow characters so they can't get where the primary victim is. (Of course, that victim has to move around occasionally.)
Make it a bad idea to bunch up around one foe.
Soldiers and Controllers can be of great help here.
Use Skirmishers or Lurkers that attack "non-bunched-up" party members that strike from range.
Brutes and Soldiers are common targets chosen by PCs. Add Artillery to make someone want to get over to them. (Artillery is really nasty if they can shoot their ranged and area bursts unmolested, but they can't take much punishment and are really pressed when a melee foe engages them.)
Use Minions. Focusing fire on a Minion is useless, of course, but if you don't take them out, their damage piles up and the party wonders where all those hit points went. (Famous Last Words: "They were just Minions!")
I remember the dreaded Irontooth encounter... The party's Paladin dropped when swarmed by several Minions, and Irontooth didn't have to do much to take him down. (Made me really appreciate Minions as a DM

). A similar encounter was with Skeleton Minions using bows.