HBase currently does not do well with anything above two or three column families so keep the number of column families in your schema low. Currently, flushing and compactions are done on a per Region basis so if one column family is carrying the bulk of the data bringing on flushes, the adjacent families will also be flushed though the amount of data they carry is small. When many column families the flushing and compaction interaction can make for a bunch of needless i/o loading (To be addressed by changing flushing and compaction to work on a per column family basis). For more information on compactions, see ???.
Try to make do with one column family if you can in your schemas. Only introduce a second and third column family in the case where data access is usually column scoped; i.e. you query one column family or the other but usually not both at the one time.
Where multiple ColumnFamilies exist in a single table, be aware of the cardinality (i.e., number of rows). If ColumnFamilyA has 1 million rows and ColumnFamilyB has 1 billion rows, ColumnFamilyA's data will likely be spread across many, many regions (and RegionServers). This makes mass scans for ColumnFamilyA less efficient.