Every user, every application takes resources. Nothing is free.
"Best off" is an interesting concept. It depends on what you mean by "best."
If you want to conserve memory and make your machine seem to be faster, then you should stick to single user at a time. One user can actually have more than one application running and will actually be more efficient at doing so because the system won't be dealing with two desktops, two set of preferences, etc, etc, etc.
And, if "Me" has admin privileges and "Guest" does not, there there is a certain risk when "Me" runs an application because "Me" may mess up the entire OS, whereas "Guest" who doesn't have those privileges, cannot.
So, "best" depends on whether you want efficiency or safety. There is a commonly accepted "best practice" that says one should rarely run in administrator role because of the risks of having that much authority. In a professional setting, I never let end users have Admin privileges, and restricted who had admin privileges to the few systems administrators I trusted with that authority.
On the other hand, in the Mac world I bet 95% of us ignore that best practice and run as admins.
Bottom line, you're more efficient and risky with one admin account, less efficient but safer with one admin and one non-admin user, running most of your stuff as the non-admin. And you are least efficient if you, as one person, open both accounts at once.
Does that help?