the following is with PvE in mind. so if you want to pvp, just ignore this post and wait for someone with experience in that.

mostly it seems to be "play the classes you like", nowadays.

i for one did that from the beginning of my boxing "career", after trying "shamans only" to get used to boxing at all. i played 3 shamans when i started boxing with my girlfriend playing another 2 of them. we did that until level 60 and then decided we would like to play our mains we played before starting to multibox.
since then our main group was dk-tank, balance-druid, arcane/frost-mage, resto-druid, bm-hunter for most of wotlk.

i started fiveboxing some time ago and what i like to do is put a group together on http://raidcomp.mmo-champion.com/ with the char/s i want in the group and then optimize either for physical buffs/debuffs or for ranged caster buffs/debuffs.

if i had no chars on a server, i probably would start a heavily optimized group for caster dps, as i find them to be easier played than melee. my group setup is like this right now: http://raidcomp.mmo-champion.com/?c=...00000000000000 - one could exchange the feral druid for a prot paladin (or any tank, for that matter) and would still have nice synergy. which is what i go for.
fyi: this team is level 83 right now, so i guess it qualifies as "at higher levels" .

also... i'm a big altoholic, so i try to go for one char of every spec and such stuff. as i wrote at the beginning - try what you would like to play =) you can always level other chars and switch some chars from your team(s)...