For the Big Guitar sound, as heard in Chris Isaak's "Wicked Game", I believe Gearslut James Calvin Willsey used a Strat plugged into a Twin Reverb, with plenty of amp 'verb.
For excellent examples of this type of tone, I strongly suggest you listen to Richard Bennett's 'Themes From a Rainy Decade". He has clips on his
MySpace site. Bennett is a master at this sound, typically a Strat or a Gretsch 6120
You can hear me attempt it
here.
Click on "These Arms of Mine", which was done with a Twin Peaks vibe. Gretsch Electromatic into 1968 Vox Cambridge Reverb with the trem and verb cranked up high.