Would a 60-40 Obama district in Orlando consistently elect Grayson? Considering how he was thrashed in 2010, I am guessing he would lose even in that Democratic of a district. Nominating Grayson again would be a mistake, even if he somehow does win that district in 2012.
I actually checked it, and an Orlando-based Dem Pack district (which is what the Republicans will probably draw since it's legal and makes all the others around it Safe R) would probably be about 70-30. The area west of Orlando is like 90% Obama (it's the part the 3rd was brought down to get) so that plus the 65% Obama parts of the city proper should be safe enough, even for a bomb-thrower like Grayson.
Granted, Republicans have won stronger D Districts, but usually against horribly corrupt incumbents. However Grayson extremely poor performance and bombastic style means Orlando might just make an exception, although said Republican would be gone the next election almost certainly. The biggest problem for Grayson will be winning the Democratic primary in what will probably be a heavily minority seat.