So which null equals this null, that null? maybe this null, or is it this null?
Tuning takes many routes and I get into some interesting situations and often make some exciting finds, see http://sqlblogcasts.com/blogs/grumpyolddba/archive/2010/05/17/just-when-you-thought-it-was-safe.aspx for an example.
Today I encountered a multitude of Foreign Key constraints on a table, now FKs are often candidates for indexes and as none of the defined keys had an index it required a closer look. I view foreign key constraints as somewhat of a pain, excessive keys can cause excessive related io, I've encountered a few cases where this happens, sadly due to the nature of client data it's not something I can publish, however examining this table I noted that all the columns were nullable, a contradiction in terms in my world unless of course you have a range of nulls! Nullable columns also create larger indexes, the main reason for my dislike of them, nulls.
Sadly of course there is another reason for adding foreign key constraints to a database and that's so you can retrospectively draw an ER diagram with the built in tools, always useful to be able to see how you put the schema together afterwards!
If you've always been wishing you had a design tool but always found them just too expensive to justify the expenditure may I recommend ModelRight 3 http://www.modelright.com/ I've been using this a while now, I admit I don't use it much as I'm supporting existing databases, but sometimes it's handy to model a set of tables when you're working with complex data sets, but no nullable foreign keys!