With Safari 5.1, Apple has changed the API (application programming interface) quite a bit. These changes have porven to be a big challenge for 3rd party developers, including the developers of Glims and 1Password, who have built their products using a now outdated API. To their credit, MacHangOut (Glims) and Agile (1Password) have done quite an amazing task of working through the compatibility and functionality issues triggered by the various API changes. Yet, more work on their part remains.
Anyone experiencing Safari 5.1 performance issues would be wise to disable all extensions in Safari Preferences>Extensions and restart Safari. If Safari is now stable, re-enable one extension at a time, then restart Safari. If stability is OK, reenable the next extension, restart Safari etc.
If performance is compromised, the last extension enabled is problematic. Disable that extension and restart Safari. Continue the enabling process.
For problematic extensions, check the developer's site for any information relative to Safari 5.1 compatibility, and also contact the developer about your findings.