For my part, I've both DMed and played with multiple PCs, although nobody ever had more than two at a time. Players that have DMed before seem to handle two PCs better than those who haven't - both in-combat and out.
I've found that it goes smoother if one or both of the PCs is low-complexity. Taking always-on flat bonuses in favour of abilities that require triggering is one way to accomplish that. In a similar vein, the higher the frequency that a given ability can be used at, the easier it tends to be to remember and to run. So anything at-will is more straightforward than encounters, which are simpler than dailies. In 3.5, fighters that specialized in a weapon were awesome as second PCs.
As a DM, one thing I've encouraged to ease roleplaying complexity is to make one character be some sort of non-sapient. Players have done some interesting things with that... I've seen pseudodragons, drakes, humanoid and four-legged constructs, guardian angels, and floating weapons. Sometimes they're statted up like the creature they chose, and other times they're done up as a regular PC and simple reskinned to the selected creature.
I've also seen it happen in both small parties and large parties. With small parties it can be a necessity to enable play at all, but I haven't found it to be a detraction for big groups. Sometimes the neatest interactions come about as a result of it...
I quite like multiple PCs, both as a player and as a DM. It's fun!
-blarg