After getting the Deepsilver Humblebundle just played Saints Row 3 for 2 days to a total of about 8 hours.
Then I played something else, restarted my PC and launched Saints Row 3 again but found out that the game now is unplayable because of a massive framerate drop.

I didn't install/change anything, Crossfire seems to work in order and as far as I know other games have not been affected.
Why did I suddenly lose 20 fps?
Did this happen to you as well?

Overheating?

That's really hard to diagnose :(

You can try turning off crossfire even if there doesn't seem to be a problem. It plays quite easily at 60fps on any modern card...

very hard to say....
overheating....if your other games are working = NO
(trotzdem es ist heiss in Deutschland, check mal die Temperatur, sieh nach ob die Lüfter evtl. verstopft sind usw.
starte ein Diagnose Prog oder nen Benchmark)

If only SR3 is running slow maybe you should check the settings for SR3....

Yeah, probably overheating.

It's not related to SR3 alone.
I've checked with Batman Arkham City, same thing, Framerate dropped to half or more.
Still Ati-Catalyst says that the fan is working at 26% of its possible power, Card has 64°C (a temperature which I've seen even during winter months)
Crossfire seems to be enable fine, I could use the "Override-Button" to manually set the 100% making the card sound like an Vacuumcleaner and dropping the temeperature to 46°C

No, according to Catalyst, it's not the heat. As I got truly horrible framerates even with full Vacuumcleanerspeed and 50°C

I wonder if something happened to directX, because with directX9 the game plays better although tests suppose that WIN7 64bit should have much better framerates with DirectX10/11

Just tested other games.
Skyrim, Dead Island and others work fine in much higher settings.
SR3 isn't even bothering to be playable in lowest settings.

It ran fine with DX11 yesterday, but today it is unplayable with DX11

hm.....How up to date are your drivers? Is Vsync enabled?

Updated ATI Catalyst after the framerate drop happened, and for Saintsrow 3 I always had Vsync disabled.
Does it have something to do with DirectX? How can I reinstall/repair that?

There should be an uninstall/repair option. If not, you might want to revert back to an older ATI Catalyst driver.

I don't think it's your video card the problem

just google the issue , you'll see the problem , is the game most of the time

Btw what your computer specs ?

I have an
i7 with 2,66 GHZ
8 GB of Ram, a
Radeon HD 5970 with 2x1GB of VRam with a
Win7 64bit OS

I had this exact same problem many months ago and the solution came courtesy Iain by changing the Data Execution Setting through my question thread at the time
http://www.gog.com/forum/general/saints_row_3_lag_anyone_got_a_solution/post15


Also as I remember while searching for a solution prior to the thread, you should turn off crossfire also - but I may not be correct on that.