I have the Pronto TSU-1000 (going to be upgrading to the 3000) and have no problems using the Pronto "one-handed". I'm just your average 5'9" geek with "normal" sized hands.

And your ideas about "activity" is spot on. I have a "Tivo living room" activity that has tivo commands, but the volume and mute control the amp (actually, mute also pauses the TiVo... just in case). I have a "Tivo bedroom" activity that has volume and mute for the TV. I even have a "TiVo/VCR" activity that has some VCR controls and some TiVo controls on one panel. This allows me to dub tapes from programs I've recorded without jumping between devices to get it done.