One free tool that will help you identify bottlenecks is Qure Analyzer:
It takes as input a trace file and runs a very deep analysis to zoom in on poorly performing SQL queries, for example by application, user, host, time or by multiple dimensions. Another nice feature is the ability to compare trace files -- very useful if you want to know how effective your tuning changes have been.
Qure Analyzer will help you find the problems, but won't tell you how to fix them. However, DBSophic also provides a (not-free) tool called Qure Optimizer that does exactly that:
It will analyze the database workload (one or more trace files) and give you specific recommendations for improving performance (eg, add/modify indexes and rewrites to SQL syntax). The tool even uses a copy of the production database to benchmark its recommendations\, so that you know what performance improvement to expect when you deploy the recommendations to production.
Hope that helps!