I would be in for a world of hurt! Way worse than if a few of my accounts were compromised because I had used the same password. But still, the chances of being compromised are probably much smaller.
I'd be interested in seeing some robust analysis of password safe software. But "Password safe" and "keepass" appear to be reputable.
I'd also like a native, and trustworthy, password safe for OS X that can work with something like Yubikey.
It does not actually save any passwords. It would replace Google Authenticator or an RSA SecurID FOB.
I know I can use LastPass with Google Authenticator to identify trusted devices. Still not perfect, but perfect security would be too inconvenient for anyone to use.
So you need your password and the Yubikey to unlock your password safe.
You could set the Yubikey up to be the password - so you only need the Yubikey to open up Keepass.
(disclaimer: I am the founder of Authy.com a two-factor auth API)
(I always thought the really smart crackers would break in, modify the application code to weaken the password encryption, and then re-encrypt every password when the user logs in. Come back a few weeks later and collect a bunch of working passwords, with nobody the wiser.)