As long as you don't go overboard, there shouldn't be any problems. I am using 4 tile mobs in my current project for particularly large beasties and haven't seen any reason not to use them. Using them for player mobs might be an issue if you anticipate many players and a lot of fiddling with overlays.

Remember that "lag" is actually much different than CPU overhead and is affected by everything from connection speed to server congestion. CPU overhead and memory use are things the game designer needs to be concerned with, as these are more or less directly under his/her control. I would be more concerned about ineffecient loops than I would multi-tiled mobs, given the loops can quickly make mincemeat of your desired effeciency!