I don't run my own installation (used the hosted one for about a year) but have seen friends upgrades go not so smoothly. In keeping with various updates I'd say it'd take a bit of time.
The only time I've had problems upgrading was when, running off the trunk svn build, a new tags system which changed a bunch of database tables was introduced and then scrapped shortly afterwards. Repairing the tables was annoying, but that's life on trunk for you; there's a reason it's not recommended for production sites. Other than that, all of my upgrades have gone smoothly. In my (anecdotal) experience, most problems with upgrades (and, indeed, most problems generally) are caused by badly written or incompatible plugins.
