I run multiple e-mail account from different suppliers; Hotmail, Outlook, Yahoo, Gmail, Supanet.
I have found both Thunderbird and Microsoft Windows Live Mail are easy to use.
Account segregation is clear; replies go out from the account they were received. For new mail, it is easy to select the account.
Thunderbird has the advantage if you want a bit more mail management in the client (timed deletion, rule based sorting to mail folders etc).
Because I see advantages in both products, I actually run both interchangeably (often simultaneously) without problems.
I am told that Thunderbird has the advantage in off-line e-mail backup... in that it is easier to move them to a new PC.