I think I might have finally discovered the holy grail for Mac users on this forum :) I've managed to get Sam and Max running on a Mac without rebooting into Windows. The game runs smoothly with no apparent graphical problems or slowdown. The launcher screen is perfect apart from the Launch Game button not appearing. Just click where the button should be and the game will launch.
You'll need CrossOver Games (http://www.codeweavers.com/products/cxgames/) to run the game. The software costs $40 but a 30-day trial is also available. On the plus side you don't need a copy of Windows to run the software so that saves a bit of money.
Here's how I got everything working:
1) Install CrossOver Games and run it.
2) Download Internet Explorer 6 from Microsoft's website (http://www.microsoft.com/windows/ie/ie6/downloads/critical/ie6sp1/default.mspx) and download a Sam and Max episode.
3) In CrossOver Games, click the Configure menu and choose 'Install Software'.
4) Click the 'Install Unsupported Software' button, follow the wizard and choose to install into a new bottle. Give the bottle a name (like 'Sam and Max') and set the bottle type to 'win98'. Click Create.
5) Click the Install button in the next screen and then locate the ie6setup.exe file you downloaded from Microsoft's website. Follow the installer, choosing to install a typical installation.
6) Click Finish when the installer is done. CrossOver will simulate a Windows reboot. Click Finished in the CrossOver window when it is done.
7) Click on the Configure Menu and choose 'Manage Bottles'. Choose the bottle you created in the left-hand list. Click the Control Panel tab on the right and double-click 'winecfg'. Set the Windows version at the bottom of the window to Windows Vista. Click OK to close the window. You can also close the Manage Bottles window.
8) To install Sam and Max, choose Install Software in the Configure menu. Click Install Unsupported Software, but this time choose to install into an existing bottle. Pick the bottle you created before. Follow the wizard and point it to the Sam and Max installer from Telltale.
9) Install the game as normal and uncheck 'Play Now' at the end of the install.
10) When CrossOver is finished installing, simply click on the Programs menu in CrossOver to launch the game. To install more episodes, just repeat step 8.
This process works perfectly on my MacBook Pro. I've only tested Abe Lincoln Must Die (Season 1) and Chariot of the Dogs (Season 2) so I'm not sure if this works for all the episodes. It'd be good to hear if it works for other people with different configurations.
Hope this helps!