I asked about the same thing on the SQLAlchemy Google group, and I got a recipe that appears to work well (all my tables are emptied). See the thread for reference.
My code (excerpt) looks like this:
import contextlib
from sqlalchemy import MetaData
meta = MetaData()
with contextlib.closing(engine.connect()) as con:
trans = con.begin()
for table in reversed(meta.sorted_tables):
con.execute(table.delete())
trans.commit()
Edit: I modified the code to delete tables in reverse order; supposedly this should ensure that children are deleted before parents.