I just upgraded from 4.x to 5.x without a problem. Only thing you might have a problem with is extensions. I am running quite a few, and they made it fine, but if you want to compare lists we can. If you have any that I have not tested you can just check on those few instead of having to check your whole list.
Like I said, my upgrade went fine. I hope yours does to.
http://luke.gedeon.name/scheduled-maintenance-2008-03-21.html
On my testing server I have PHP 5.2.5, but on my live server I have 4.4.8. I move plugins back and forth between them constantly and I don’t think I have ever had an issue.
Based on the advice here, I went ahead and had my domain server host change me to a server with PHP v5.2.5 and MySQL v5.0.45 and I didn’t do a thing, except request a nameserver change with my registrar. My site looks as it did before, no problems whatsoever. Thanks for the assurance!