A good map of Malta is essential. Signage is not great but not abysmal (try southern Italy for that) so knowing where you're going (i.e., towns/neighbourhoods along the way) is essential. Didn't have too much of a problem driving in from MLA after midnight but finding the hotel once one got to St. Juliens wasn't that easy (turnoffs aren't well-marked). Maltese roads aren't in very good shape so the rentals seem to be 2-3x more beaten up compared to cars of similar usage elsewhere. Never noticed driving to be that bad (what the earlier poster said could be said of New Orleans).

Be careful of the numerous speed cams too.