Trying to program an FPGA. (Altera Cyclone II)
Make sure you have selected the proper programming hardware by clicking 'Hardware Setup...' (e.g. 'USB-Blaster').
Select the proper 'Mode' from the dropdown based on what your target board supports.
For Active Serial Programming, click 'Add File...' and select the .pof file (I think the dialog forces this). JTAG and Passive Serial modes use .sof files.
For Active Serial Programming, click 'Add Device...' to select the EPCS configuration device you're using (e.g. EPCS4).
Finally, check 'Program/Configure' checkbox and should now be able to click 'Start'.


UPDATE: Verify the USB-Blaster driver is installed; should show up as 'Altera USB-Blaster' in Device Manager when the DE2 board is on and plugged in: