I did not have any issues when I upgraded. Just make sure all of your licensed software is compatible and that the vendors supply you with a new license key for V5R4; upgrade fees may apply.
I upgraded 2 i5′s in early February 2009, no issues.
I’ve perfomed a few dozen V5R3 to V5R4 upgrades over the last couple of years.
Best advice I have is to install the most current V5R3 CUM PTFs before you start into V5R4.
We’d have issues with every 3rd or 4th upgrade until we started doing this.
Deleting you old (Junk) spool files is a good idea too. They can take hours to convert if you have loads of them.