We have 2, then 3 data centers, and we are running a few hundred instances of MySQL in a about a dozen of replication chains in 2011.
It begins to hurt, quite a bit.
EDIT: There is also the move to InnoDB, which was met with a lot of scepticism:
- Uses more disk space
- Couldn't easily detach and attache tablespaces
- Broke merge tables, which we used a LOT in dw.
but
20.000 writes/s instead of 7000 writes/s.