Should frequently accessed tables containing large blobs with one-to-one relationships be normalized and columns split into two tables?
Using InnoDB and the Barracuda file format permits you to deploy the Dynamic row_format. This configuration will aid you due to the way it will store the BLOBs off page. Queries not using the columns with the BLOBs shouldn't need to touch their pages;

http://dev.mysql.com/doc/innodb-plugin/1.0/en/innodb-row-format-dynamic.html